diff --git a/.gitattributes b/.gitattributes index f997e0d2637d31f05ee0245ed69df4b9fdb8943d..73f21a3be72f2c98f9caede304cbc2cbe6a14ecb 100644 --- a/.gitattributes +++ b/.gitattributes @@ -88,3 +88,18 @@ Exp-1/Input_Models/Uni[[:space:]](S-R)/visualizations/diagnostics_example_16/ste Exp-1/Input_Models/Uni[[:space:]](S-R)/visualizations/diagnostics_example_16/step3_contextualized_similarities.png filter=lfs diff=lfs merge=lfs -text Exp-1/Input_Models/Uni[[:space:]](S-R)/visualizations/diagnostics_example_16/step4_refined_similarities.png filter=lfs diff=lfs merge=lfs -text Exp-1/Input_Models/Uni[[:space:]](S-R)/visualizations/diagnostics_example_16/step5_final_pair_scores.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/training_plots/sentence-transformers_embeddinggemma-300m-medical_batch_losses_epoch_21.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/training_plots/sentence-transformers_embeddinggemma-300m-medical_batch_losses_heatmap.pdf filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/training_plots/sentence-transformers_embeddinggemma-300m-medical_batch_losses_heatmap.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/training_plots/sentence-transformers_embeddinggemma-300m-medical_final_training_curves.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/training_plots/sentence-transformers_embeddinggemma-300m-medical_training_loss.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/training_plots/sentence-transformers_embeddinggemma-300m-medical_validation_accuracy.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/visualizations/comprehensive_analysis_example_1.pdf filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/visualizations/comprehensive_analysis_example_1.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/visualizations/diagnostics_example_1/step1_raw_similarities.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/visualizations/diagnostics_example_1/step2_forward_attention.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/visualizations/diagnostics_example_1/step3_reverse_attention.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/visualizations/diagnostics_example_1/step4_contextualized_similarities.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/visualizations/diagnostics_example_1/step5_refined_similarities.png filter=lfs diff=lfs merge=lfs -text +Exp-2/models/LOKI/visualizations/diagnostics_example_1/step6_final_pair_scores.png filter=lfs diff=lfs merge=lfs -text diff --git a/Exp-2/models/CMDL/README.md b/Exp-2/models/CMDL/README.md new file mode 100644 index 0000000000000000000000000000000000000000..3608cbfd84e3e79343cf5cdc72a78d4b4595a4b2 --- /dev/null +++ b/Exp-2/models/CMDL/README.md @@ -0,0 +1,6 @@ +# CMDL Model Checkpoints + +Place the following files here (from `CMDL/output_cmdl_mimic/models/`): + +- `text_enet_best.pt` — Trained text EncoderNet +- `col_enet_best.pt` — Trained column EncoderNet diff --git a/Exp-2/models/CMDL/col_enet_best.pt b/Exp-2/models/CMDL/col_enet_best.pt new file mode 100644 index 0000000000000000000000000000000000000000..5024b0e57e6e5d3d5f358a2d31df01cb182ede43 --- /dev/null +++ b/Exp-2/models/CMDL/col_enet_best.pt @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:b4eff4ec751195c065b842e1277981f0d2d7619670cbbb446f802ded933189bf +size 494071 diff --git a/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim b/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim new file mode 100644 index 0000000000000000000000000000000000000000..593f645d5e5952a84fa1d0cb98bd6240a45eb14f --- /dev/null +++ b/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:0a6c72484f1ad251bbcef54add90e9dcd0d2d24316c61aa28178af89a82a8920 +size 67059308 diff --git a/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim.vectors_ngrams.npy b/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim.vectors_ngrams.npy new file mode 100644 index 0000000000000000000000000000000000000000..e77fe52f20d2499cbeeaaba03c239d0b599344ca --- /dev/null +++ b/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim.vectors_ngrams.npy @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:d05df0ab4b2ff1b46d5e668f4397af3f69b57af65668a2341a1a994b9c306417 +size 2400000128 diff --git a/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim.vectors_vocab.npy b/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim.vectors_vocab.npy new file mode 100644 index 0000000000000000000000000000000000000000..c2d78549af519a36257c94cc124d1882ac0721ee --- /dev/null +++ b/Exp-2/models/CMDL/resources/fasttext/cc/cc.en.300.gensim.vectors_vocab.npy @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:783030c2a62aa08fce0c18cff459ded2ef8a9306ea4456dd25dda767006e4db6 +size 2400000128 diff --git a/Exp-2/models/CMDL/text_enet_best.pt b/Exp-2/models/CMDL/text_enet_best.pt new file mode 100644 index 0000000000000000000000000000000000000000..4ef8369a5f8864cd9ea2c9c0e05c6d5a90ca794f --- /dev/null +++ b/Exp-2/models/CMDL/text_enet_best.pt @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:93ba6aef71dceb6b75b7dd524ea357588ed258e6f358aac2ec8e981f8b2accdf +size 494093 diff --git a/Exp-2/models/LOKI/args.json b/Exp-2/models/LOKI/args.json new file mode 100644 index 0000000000000000000000000000000000000000..655595b343ec1cddb16af3012f06886b06909f71 --- /dev/null +++ b/Exp-2/models/LOKI/args.json @@ -0,0 +1,168 @@ +{ + "model_key": "google", + "use_bidirectional": true, + "attention_direction": "row_to_sentence", + "use_flash_attention": false, + "use_unsloth": true, + "unsloth_full_finetuning": false, + "unsloth_4bit": false, + "unsloth_qlora": false, + "unsloth_qlora_rank": 32, + "unsloth_qlora_alpha": 64.0, + "unsloth_target_modules": "auto", + "unsloth_pooling_mode": "mean", + "override_embedding_dim": 0, + "override_max_seq_length": 0, + "start_training_from_stage": 1, + "enable_lora": false, + "disable_lora": true, + "encoder_only_training": false, + "use_cache": true, + "stage0_cache_mode": "off", + "encoder_tuning_mode": "gradual", + "gradual_unfreeze_initial_layers": 2, + "gradual_unfreeze_every": 1, + "gradual_unfreeze_max_layers": 6, + "gradual_unfreeze_include_pooler": true, + "train_file": "/run/media/crusnic/OTHER/LOKI_Git_VLDB/Datasets/pharma_flipped_structured/train_row_level.json", + "eval_file": "/run/media/crusnic/OTHER/LOKI_Git_VLDB/Datasets/pharma_flipped_structured/val_row_level.json", + "test_file": "/run/media/crusnic/OTHER/LOKI_Git_VLDB/Datasets/pharma_flipped_structured/test_row_level.json", + "output_dir": "./output_pharma_flipped_model/", + "task_direction": "DOC_TO_TABLE", + "native_direction": "DOC_TO_TABLE", + "dataset_format": "other", + "max_train_examples": 0, + "max_eval_examples": 0, + "eval_every_n_steps": 0, + "epochs": 20, + "early_stopping_patience": 50, + "early_stopping_min_epochs": 50, + "enable_checkpointing": true, + "lr": 0.0001, + "encoder_lr": 1e-05, + "lr_scheduler_type": "cosine", + "lr_num_cycles": 1, + "min_lr_ratio": 0.1, + "train_batch_size": 64, + "eval_batch_size": 64, + "encoding_batch_size": 64, + "weight_decay": 0.01, + "warmup_ratio": 0.1, + "max_grad_norm": 1.0, + "gradient_accumulation_steps": 1, + "mix_examples": false, + "triplet_strategy": "full", + "max_triplets_per_example": 2, + "loss_type": "bidirectional_triplet", + "use_wandb": false, + "use_cross_attention_lora": false, + "lora_rank": 128, + "lora_alpha": 512, + "lora_dropout": 0.1, + "do_visualize": true, + "do_clean_analysis": false, + "visualize_examples": "1", + "normalize_attention": true, + "skip_four_stage_viz": true, + "aggregation_method": "top_k_pairs", + "top_k": 5, + "norm_type": "rmsnorm", + "use_qk_rmsnorm": false, + "use_latent_bottleneck": false, + "latent_num": 64, + "latent_dropout": 0.0, + "pair_topk_mask": false, + "pair_topk_k": 0, + "use_hard_negative_mining": true, + "hard_negative_topk": 1, + "margin": 0.3, + "scale": 10.0, + "pair_margin": 0.3, + "margin_end": 0.5, + "margin_schedule": "none", + "ranking_loss_type": "infonce", + "infonce_tau": 0.2, + "triplet_weight": 0.5, + "attention_loss_weight": 0.0, + "pair_loss_weight": 0.3, + "diversity_weight": 0.0, + "direct_attention_loss_weight": 0.0, + "direct_attention_diversity_weight": 1.0, + "direct_attention_hub_weight": 0.0, + "direct_attention_entropy_weight": 0.0, + "direct_attention_entropy_floor_ratio": 0.5, + "forward_attention_loss_weight": 0.0, + "pair_mil_loss_weight": 0.0, + "pair_mil_positive_margin": 0.2, + "pair_mil_negative_margin": 0.05, + "pair_mil_sparsity_weight": 0.0, + "pair_mil_hub_weight": 0.0, + "use_attention_distillation": true, + "distillation_weight": 0.2, + "teacher_temperature": 0.5, + "student_temperature": 0.1, + "distillation_loss_type": "js_div", + "teacher_hub_centering": true, + "sigreg_weight": 0.15, + "sigreg_target_std": 1.0, + "sigreg_num_proj": 1024, + "sigreg_knots": 17, + "sinkhorn_weight": 0.05, + "pair_score_method": "cosine", + "share_attention_weights": true, + "extract_join_paths": true, + "join_path_threshold": 0.15, + "use_refinement": false, + "skip_ffn": true, + "use_self_attention": false, + "self_attention_heads": 1, + "self_attention_dropout": 0.1, + "attention_type": "top_k_sparse", + "use_header_conditioning": false, + "use_cell_level_matching": false, + "cell_matching_weight": 0.35, + "cell_matching_pooling": "max", + "cell_row_fusion_weight": 0.15, + "use_gated_attention": true, + "gated_attention_mode": "vector", + "gated_attention_hidden_dim": 0, + "gated_attention_dropout": 0.0, + "gated_attention_init_bias": 0.0, + "use_inner_gate": true, + "disable_temperature": true, + "attention_activation": "softmax", + "attention_alpha": 1.5, + "sparse_top_k": 5, + "window_size": 5, + "threshold_base": 0.3, + "init_method": "orthogonal", + "init_method_params": { + "q_gain": 0.5, + "k_gain": 0.5, + "v_gain": 1.0, + "bias_std": 0.02 + }, + "init_show_descriptions": false, + "enable_training_curves": true, + "track_batch_losses": true, + "track_val_loss": true, + "auto_plot_curves": false, + "enable_row_sent_eval": true, + "row_sent_test_file": "/run/media/crusnic/OTHER/LOKI_Git_VLDB/Datasets/pharma_flipped_structured/test_row_level.json", + "row_sent_annotation_file": "/run/media/crusnic/OTHER/LOKI_Git_VLDB/Datasets/pharma_flipped_structured/Annotated_Test.json", + "row_sent_max_examples": null, + "enable_attention_diagnostics": true, + "attention_diagnostic_examples": 3, + "save_best_by_test_metrics": true, + "verbosity": 1, + "quiet": false, + "verbose": false, + "use_compile": false, + "compile_mode": "reduce-overhead", + "verbose_flag": true, + "extra_verbose": false, + "model_name": "sentence-transformers/embeddinggemma-300m-medical", + "architecture": "bidirectional", + "embedding_dim": 768, + "max_seq_length": 512 +} \ No newline at end of file diff --git a/Exp-2/models/LOKI/extracted_join_paths.json b/Exp-2/models/LOKI/extracted_join_paths.json new file mode 100644 index 0000000000000000000000000000000000000000..de69d48d055bc3046edabe937022fb67202ed0fb --- /dev/null +++ b/Exp-2/models/LOKI/extracted_join_paths.json @@ -0,0 +1,12310 @@ +[ + { + "example_idx": 0, + "anchor_id": 7299990219575238449, + "positive_id": 2274888708328402113, + "join_paths": [ + [ + 5, + 29, + 0.32421875 + ], + [ + 5, + 15, + 0.30078125 + ], + [ + 3, + 29, + 0.298828125 + ], + [ + 0, + 29, + 0.2890625 + ], + [ + 1, + 29, + 0.283203125 + ] + ], + "rows": [ + "The affinity of eletriptan ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1H-indole) for a range of 5-HT receptors was compared to values obtained for other 5-HT1B/1D receptor agonists known to be effective in the treatment of migraine.", + "Eletriptan, like sumatriptan, zolmitriptan, naratriptan and rizatriptan had highest affinity for the human 5-HT1B, 5-HT1D and putative 5-ht1f receptor.", + "Kinetic studies comparing the binding of [3H]eletriptan and [3H]sumatriptan to the human recombinant 5-HT1B and 5-HT1D receptors expressed in HeLa cells revealed that both radioligands bound with high specificity (>90%) and reached equilibrium within 10-15 min.", + "However, [3H]eletriptan had over 6-fold higher affinity than [3H]sumatriptan at the 5-HT1D receptor (K(D)): 0.92 and 6.58 nM, respectively) and over 3-fold higher affinity than [3H]sumatriptan at the 5-HT1B receptor (K(D): 3.14 and 11.07 nM, respectively).", + "Association and dissociation rates for both radioligands could only be accurately determined at the 5-HT1D receptor and then only at 4 degrees C. At this temperature, [3H]eletriptan had a significantly (P<0.05) faster association rate (K(on) 0.249 min(-1) nM(-1)) than [3H]sumatriptan (K(on) 0.024 min(-1) nM(-1)) and a significantly (P<0.05) slower off-rate (K(off) 0.027 min(-1) compared to 0.037 min(-1) for [3H]sumatriptan).", + "These data indicate that eletriptan is a potent ligand at the human 5-HT1B, 5-HT1D, and 5-ht1f receptors and are consistent with its potent vasoconstrictor activity and use as a drug for the acute treatment of migraine headache.", + "Animals\nBinding, Competitive\nCOS Cells\nCell Line\nCold Temperature\nHeLa Cells\nHumans\nIndoles\nKinetics\nOxazoles\nOxazolidinones\nPiperidines\nPyrrolidines\nRadioligand Assay\nReceptor, Serotonin, 5-HT1B\nReceptor, Serotonin, 5-HT1D\nReceptors, Serotonin\nSumatriptan\nTriazoles\nTritium\nTryptamines" + ], + "sentences": [ + "name: Apo-zolmitriptan Rapid; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Act Rizatriptan; ingredients: Rizatriptan; parent_key: DB00953.", + "name: AVON HeXashield Pain Relief for Muscle, Back and Joint Cream; ingredients: Levomenthol + Methyl salicylate + Synthetic camphor; parent_key: DB00825.", + "name: Jamp Zolmitriptan; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Auro-rizatriptan; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Jamp-zolmitriptan; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Mylan-rizatriptan ODT; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Apo-zolmitriptan; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Auro-eletriptan; ingredients: Eletriptan; parent_key: DB00216.", + "name: Sandoz Zolmitriptan ODT; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: PMS-zolmitriptan ODT; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Teva-zolmitriptan; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Dom-zolmitriptan ODT; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Shopko Ice Mint; ingredients: Eucalyptol + Levomenthol + Methyl salicylate + Thymol; parent_key: DB03852.", + "name: Naratriptan Hydrochloride; ingredients: Naratriptan; parent_key: DB00952.", + "name: Eletriptan Hydrobromide; ingredients: Eletriptan; parent_key: DB00216.", + "name: Apo-naratriptan; ingredients: Naratriptan; parent_key: DB00952.", + "name: Maxalt Rpd; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Teva-naratriptan; ingredients: Naratriptan; parent_key: DB00952.", + "name: Zomig Zmt; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Naratriptan; ingredients: Naratriptan; parent_key: DB00952.", + "name: Apo-eletriptan; ingredients: Eletriptan; parent_key: DB00216.", + "name: Riva-rizatriptan ODT; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Mylan-zolmitriptan; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Ipg-rizatriptan; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Nra-zolmitriptan; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Mylan-rizatriptan; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Atomic Balm; ingredients: Capsaicin + Methyl salicylate; parent_key: DB06774.", + "name: Jamp-rizatriptan ODT; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Eletriptan; ingredients: Eletriptan; parent_key: DB00216.", + "name: Ratio-zolmitriptan Ir; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Dom-rizatriptan Rdt; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Menthocin Patch with Lidocaine - Strong; ingredients: Capsaicin + Levomenthol + Lidocaine + Methyl salicylate; parent_key: DB06774.", + "name: TENHEALER Pain Rub; ingredients: Dimethyl sulfone + Levomenthol + Methyl salicylate + Synthetic camphor; parent_key: DB09543.", + "name: Teva-eletriptan; ingredients: Eletriptan; parent_key: DB00216.", + "name: Rizatriptan Benzoate; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Nat-rizatriptan ODT; ingredients: Rizatriptan; parent_key: DB00953.", + "name: PMS-rizatriptan Rdt; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Zolmitriptan-odt; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Sandoz Naratriptan; ingredients: Naratriptan; parent_key: DB00952.", + "name: Zolmitriptan OD; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Oral Dent Citrus; ingredients: Eucalyptol + Levomenthol + Methyl salicylate + Thymol; parent_key: DB02513.", + "name: Gd-eletriptan; ingredients: Eletriptan; parent_key: DB00216.", + "name: Q-rizatriptan ODT; ingredients: Rizatriptan; parent_key: DB00953.", + "name: Teva-zolmitriptan OD; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Ipg-zolmitriptan; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Dom-zolmitriptan; ingredients: Zolmitriptan; parent_key: DB00315.", + "name: Trypsin Complex; ingredients: Balsam of Peru + Castor oil + Trypsin; parent_key: DB11113.", + "name: Pommade Au The Des Bois; ingredients: Camphor + Eucalyptol + Levomenthol + Methyl salicylate; parent_key: DB03852.", + "name: Cool Mint Antiseptic Mouthwash; ingredients: Ethanol + Eucalyptus oil + Methyl salicylate + Thymol; parent_key: DB02513." + ] + }, + { + "example_idx": 1, + "anchor_id": 17843781795205441407, + "positive_id": 1094194020537635993, + "join_paths": [ + [ + 9, + 7, + 0.162109375 + ] + ], + "rows": [ + "Fexofenadine, a nonsedating antihistamine, does not undergo significant metabolic biotransformation.", + "Accordingly, it was hypothesized that uptake and efflux transporters could be importantly involved in the drug's disposition.", + "Utilizing a recombinant vaccinia expression system, members of the organic anion transporting polypeptide family, such as the human organic anion transporting polypeptide (OATP) and rat organic anion transporting polypeptides 1 and 2 (Oatp1 and Oatp2), were found to mediate [(14)C]fexofenadine cellular uptake.", + "On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (NTCP) and the rat organic cation transporter rOCT1 did not exhibit such activity.", + "P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a polarized epithelial cell line lacking P-gp, and the derivative cell line (L-MDR1), which overexpresses P-gp.", + "In addition, oral and i.v.", + "administration of [(14)C]fexofenadine to mice lacking mdr1a-encoded P-gp resulted in 5- and 9-fold increases in the drug's plasma and brain levels, respectively, compared with wild-type mice.", + "Also, a number of drug inhibitors of P-gp were found to be effective inhibitors of OATP.", + "Because OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine's disposition and suggests potentially similar roles in the disposition of other xenobiotics.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAnimals\nAnion Transport Proteins\nBiological Transport, Active\nCaco-2 Cells\nCarrier Proteins\nGenes, MDR\nHeLa Cells\nHistamine H1 Antagonists\nHumans\nLLC-PK1 Cells\nMice\nRats\nSwine\nTerfenadine\nTissue Distribution\nTransfection\nVaccinia virus" + ], + "sentences": [ + "id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB00958.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 23; parent_key: DB04348.", + "id: BE0004769; name: Y+L amino acid transporter 1; organism: Humans; known_action: unknown; position: 6; parent_key: DB00130.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 9; parent_key: DB09100.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB00091.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 12; parent_key: DB00795.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 11; parent_key: DB14761.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 16; parent_key: DB13943.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13944.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: no; position: 6; parent_key: DB01117.", + "id: BE0003666; name: Copper-transporting ATPase 1; organism: Humans; known_action: no; position: 10; parent_key: DB09130.", + "id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: no; position: 11; parent_key: DB09130.", + "id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB01586.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 3; parent_key: DB01098.", + "id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 3; parent_key: DB02123.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 1; parent_key: DB13153.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 1; parent_key: DB00887.", + "id: BE0004769; name: Y+L amino acid transporter 1; organism: Humans; known_action: unknown; position: 11; parent_key: DB08838.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB01586.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 4; parent_key: DB02123.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00945.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 20; parent_key: DB00328.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 12; parent_key: DB01098.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB01244.", + "id: BE0003666; name: Copper-transporting ATPase 1; organism: Humans; known_action: unknown; position: 15; parent_key: DB00526.", + "id: BE0000106; name: Solute carrier family 22 member 5; organism: Humans; known_action: unknown; position: 1; parent_key: DB01208.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 5; parent_key: DB08912.", + "id: BE0001134; name: Solute carrier family 15 member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB01140.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 11; parent_key: DB06290.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13946.", + "id: BE0003645; name: Solute carrier family 22 member 8; organism: Humans; known_action: unknown; position: 11; parent_key: DB02659.", + "id: BE0009872; name: Y+L amino acid transporter 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB00130.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 8; parent_key: DB01583.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00451.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 9; parent_key: DB08860.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 12; parent_key: DB01032.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13943.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB00286.", + "id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 4; parent_key: DB00787.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00646.", + "id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB04348.", + "id: BE0009680; name: B-cell antigen receptor complex-associated protein beta chain; organism: Humans; known_action: unknown; position: 2; parent_key: DB12240.", + "id: BE0000106; name: Solute carrier family 22 member 5; organism: Humans; known_action: unknown; position: 3; parent_key: DB14754.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 7; parent_key: DB09102.", + "id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB00091.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB00279.", + "id: BE0003642; name: Solute carrier organic anion transporter family member 1A2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00635.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB00396.", + "id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 2; parent_key: DB00977.", + "id: BE0000732; name: Sodium/potassium-transporting ATPase subunit alpha-1; organism: Humans; known_action: unknown; position: 2; parent_key: DB14500." + ] + }, + { + "example_idx": 2, + "anchor_id": 14990783024646610885, + "positive_id": 3489943661074987178, + "join_paths": [ + [ + 0, + 7, + 0.271484375 + ], + [ + 4, + 2, + 0.2373046875 + ], + [ + 1, + 38, + 0.232421875 + ], + [ + 9, + 2, + 0.228515625 + ], + [ + 6, + 20, + 0.2275390625 + ] + ], + "rows": [ + "BACKGROUND: Coadministration of phentermine and fenfluramine (phen/fen) effectively treats obesity and possibly addictive disorders.", + "The association of fenfluramine and certain other anorexic agents with serious side effects, such as cardiac valvulopathy and primary pulmonary hypertension (PPH), limits the clinical utility of these drugs.", + "Development of new medications that produce neurochemical effects like phen/fen without causing unwanted side effects would be a significant therapeutic breakthrough.", + "METHODS AND RESULTS: We tested the hypothesis that fenfluramine (and other anorexic agents) might increase the risk of PPH through interactions with serotonin (5-HT) transporters.", + "Because 5-HT transporter proteins in the lung and brain are identical, we examined, in rat brain, the effects of selected drugs on 5-HT efflux in vivo and monoamine transporters in vitro as a generalized index of transporter function.", + "Our data show that drugs known or suspected to increase the risk of PPH (eg, aminorex, fenfluramine, and chlorphentermine) are 5-HT transporter substrates, whereas drugs that have not been shown to increase the risk of PPH are less potent in this regard.", + "CONCLUSIONS: We speculate that medications that are 5-HT transporter substrates get translocated into pulmonary cells where, depending on the degree of drug retention, their intrinsic drug toxicity, and individual susceptibility, PPH could develop as a response to high levels of these drugs or metabolites.", + "Emerging evidence suggests that it is possible to develop transporter substrates devoid of adverse side effects.", + "Such medications could have therapeutic application in the management of obesity, drug dependence, depression, and other disorders.", + "Aminorex\nAnimals\nAppetite Depressants\nBrain\nCarrier Proteins\nChlorphentermine\nDopamine\nFenfluramine\nHypertension, Pulmonary\nMale\nMembrane Glycoproteins\nMembrane Transport Proteins\nMicrodialysis\nNerve Tissue Proteins\nRats\nRats, Sprague-Dawley\nSerotonin\nSerotonin Plasma Membrane Transport Proteins" + ], + "sentences": [ + "drugbank_id: DB14473; indication: Beroctocog alfa is indicated for the prevention and control of bleeding in patients with hemophilia A or acquired Factor VIII (FVIII) deficiency.[L11752] It is also indicated for surgical/invasive procedures in adult and pediatric patients with von Willebrand Disease in who desmopression is either ineffective or contraindicated.[L11752] It is not indicated for patients with severe (i.e. type 3) von Willebrand Disease whom are undergoing major surgery.[L11752]; _drug_name: Beroctocog alfa.", + "drugbank_id: DB00735; indication: For the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Epidermophyton floccosum.; pharmacodynamics: Naftifine is a synthetic, broad spectrum, antifungal agent and allylamine derivative. The following in vitro data are available, but their clinical significance is unknown. Naftifine has been shown to exhibit fungicidal activity in vitro against a broad spectrum of organisms including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum canis, Microsporum audouini, and Microsporum gypseum; and fungistatic activity against Candida species including Candida albicans. However it is only used to treat the organisms listed in the indications.; mechanism_of_action: Although the exact mechanism of action against fungi is not known, naftifine appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene 2,3-epoxidase. This inhibition of enzyme activity results in decreased amounts of sterols, especially ergosterol, and a corresponding accumulation of squalene in the cells.; absorption: Following single topical applications of 3H-labeled naftifine gel 1% to the skin of healthy subjects, up to 4.2% of the applied dose was absorbed.; half_life: Approximately 2 to 3 days following topical administration.; route_of_elimination: Naftifine and/or its metabolites are excreted via the urine and feces with a half-life of approximately two to three days.; _drug_name: Naftifine.", + "drugbank_id: DB05205; indication: Anxiety Disorders I,\nDepression I; mechanism_of_action: This drug increases the levels of three vital neurotransmitters that affect mood and anxiety: serotonin, norepinephrine and dopamine.; _drug_name: CX157.", + "drugbank_id: DB00918; indication: For the treatment of acute migraine headache in adults; pharmacodynamics: Almotriptan is a selective 5-hydroxytryptamine receptor subtype agonist indicated for the acute treatment of migraine attacks with or without aura in adults. Almotriptan is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Almotriptan is an agonist for a vascular 5-hydroxytryptamine receptor subtype (probably a member of the 5-HT1D family) having only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Almotriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Almotriptan in humans.; mechanism_of_action: Almotriptan binds with high affinity to human 5-HT1B and 5-HT1D receptors leading to cranial blood vessel constriction.; half_life: 3-4 hours; protein_binding: 35%; route_of_elimination: Almotriptan is eliminated primarily by renal excretion (about 75% of the oral dose), with approximately 40% of an administered dose excreted unchanged in urine. Approximately 13% of the administered dose is excreted via feces, both unchanged and metabolized.; volume_of_distribution: * 180 to 200 L; clearance: * 57 L/h [healthy]\n* 34.2 L/h [moderate renal impairment (creatinine clearance between 31 and 71 mL/min)]\n* 9.8 L/h [severe renal impairment (creatinine clearance between 10 and 30 mL/min)]; _drug_name: Almotriptan.", + "drugbank_id: DB00998; indication: For the acute treatment of migraine attacks with or without aura in adults.; pharmacodynamics: Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT1B and 5-HT1D receptors. It is structurally distinct from, but pharmacologically related to other selective 5-HT1B/1D receptor agonists. Frovatriptan has no significant effects on GABAA mediated channel activity and has no significant affinity for benzodiazepine binding sites. Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. Research has shown that migraine can be caused by the swelling of blood vessels around the brain. Frovatriptan eases the pain associated with migraine by narrowing these blood vessels. Frovatriptan has one of the highest affinities for the 5-HT1B of the second-generation triptan agonists.; mechanism_of_action: Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.; toxicity: There is no direct experience of any patient taking an overdose of Frovatriptan. The maximum single dose of frovatriptan given to male and female patients with migraine was 40 mg (16 times the clinical dose) and the maximum single dose given to healthy male subjects was 100 mg (40 times the clinical dose) without significant adverse events.; metabolism: In vitro, cytochrome P450 1A2 appears to be the principal enzyme involved in the metabolism of frovatriptan to several metabolites including hydroxylated frovatriptan, N-acetyl desmethyl frovatriptan, hydroxylated N-acetyl desmethyl frovatriptan and desmethyl frovatriptan, and several other minor metabolites. Desmethyl frovatriptan has lower affinity for 5-HT1B/1D receptors compared to the parent compound. The N-acetyl desmethyl metabolite has no significant affinity for 5-HT receptors. The activity of the other metabolites is unknown.; absorption: Frovatriptan is rapidly absorbed from the duodenum, but has low oral bioavailability.; half_life: 26 hours; protein_binding: Binding to serum proteins is low (approximately 15%). Reversible binding to blood cells at equilibrium is approximately 60%.; route_of_elimination: Radiolabeled compounds excreted in urine were unchanged frovatriptan, hydroxylated frovatriptan, N-acetyl desmethyl frovatriptan, hydroxylated N-acetyl desmethyl frovatriptan and desmethyl frovatriptan, together with several other minor metabolites. Less than 10% of frovatriptan was excreted in urine after an oral dose.; volume_of_distribution: * 4.2 L/kg [males]\n* 3 L/kg [females]; clearance: * 220 mL/min [male receiving IV dose of 0.8 mg]\n* 130 mL/min [Female receiving IV dose of 0.8 mg]; _drug_name: Frovatriptan.", + "drugbank_id: DB05100; indication: Investigated for use/treatment in brain cancer, lung cancer, and prostate cancer.; half_life: 2-5 hours; _drug_name: Prinomastat.", + "drugbank_id: DB09307; indication: Investigated for the treatment of depression.; _drug_name: Oxaprotiline.", + "drugbank_id: DB00191; indication: Phentermine is indicated, alone or in combination with topiramate, as a short-term adjunct, not pass a few weeks, in a regimen of weight reduction based on exercise, behavioral modifications and caloric restriction in the management of exogenous obesity for patients with an initial body mass index (BMI) greater than 30 kg/m2 or greater than 27 kg/m2 in presence of other risk factors such as controller hypertension, diabetes or hyperlipidemia.[FDA label]\n\nExogenous obesity is considered when the overweight is caused by consuming more food than the person activity level warrants. This condition commonly causes an increase in fat storage. It is an epidemic condition in the United States where over two-thirds of adults are overweight or obese and one in three Americans is obese. In the world, the incidence of obesity has nearly doubled.[A174391]; pharmacodynamics: It is reported that the main mechanism of action of phentermine is the generation of appetite suppression, maybe due to the increase in leptin, but it is considered that other mechanisms should be involved.[A174370] Some reports have indicated that the weight loss effect is mainly due to the increase in resting energy expenditure.[A174367]\n\nIn clinical studies where phentermine was used as a monotherapy and as combination therapy, this drug has shown an average weight loss of 3.6 kg when compared with the placebo in 2-24 weeks. Patients treated with phentermine also showed increased maintenance of the weight after treatment discontinuation.[A174367] As well, even though it is a derivative of the amphetamines, it has not been registered to produce any of the effects of amphetamine such as central nervous system stimulation, elevation of blood pressure, tachyphylaxis or QTc prolongation.[A174370]; mechanism_of_action: Phentermine is an indirect-acting sympathomimetic agent that acts by releasing noradrenaline from the presynaptic vesicles in the lateral hypothalamus. This increase in noradrenaline concentration in the synaptic cleft results in the stimulation of beta2-adrenergic receptors.[A174367] Phentermine is classified as an indirect sympathomimetic due to the increase in the level of norepinephrine, dopamine and its indirect effect towards serotonin.[L5233] Some reports have indicated that phentermine inhibits the neuropeptide Y which is a principal signaling pathway for the induction of hunger.[T403] This combined effect produces a continuous flight-or-fight response in the body which reduces the hunger signal as this state is on the immediate need for energy.[T403]\n\nLastly, some reports have indicated that phentermine is a weak inhibitor of monoamine oxidase but this mechanism does not tend to produce a clinically significant response.[T49]; toxicity: The reported LD50 after oral administration of phentermine in rats is reported to be of 151 mg/kg.[L5239] Reports of acute overdose include restlessness, tremors, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations and panic state followed by fatigue, and depression. In the cardiovascular system, there are reports of tachycardia, arrhythmia, hypertension, hypotension, circulatory collapse. In the GI tract, there are symptoms of nausea, vomiting, diarrhea and abdominal cramps. The management of acute overdosage includes symptomatic treatment as well as lavage and sedation with barbiturates.[FDA label]\n\nOn the other hand, chronic overdosage is marked by dermatoses, insomnia, irritability, hyperactivity and personality changes. In severe cases, it can derive into a schizophrenia-like psychosis.[FDA label]\n\nStudies regarding the carcinogenic potential have not been performed. On the case of mutagenic assays, phentermine was shown to not be mutagenic nor clastogenic.[FDA label]; metabolism: Phentermine undergoes minimal p-hydroxylation, N-oxidation and N-hydroxylation followed by conjugation. The total proportion of the drug that goes under metabolism only represents about 6% of the administered dose where about 5% is represented by the N-oxidized and N-Hydroxylated metabolites.[T49]; absorption: Phentermine shows a dose-dependent pharmacokinetic profile. After oral administration of a dose of 15 mg, the maximal concentration was achieved after 6 hours and its bioavailability was not affected by the consumption of high-fat meals.[A174370] The reported plasma concentration at steady-state is of around 200 ng/ml as observed in clinical trials.[T49]; half_life: The mean terminal half-life of phentermine is reported to be of approximately 20 hours.[A174370] In conditions where there is acidic urine (pH <5), the elimination half-life is of 7-8 hours.[T49]; protein_binding: The protein binding of phentermine is determined to be of 17.5%.[A174370]; route_of_elimination: Phentermine is excreted mainly in the urine from which about 70-80% of the administered dose can be found as the unchanged drug.[A174370]; volume_of_distribution: The reported volume of distribution for phentermine is reported to be of 5 L/kg.[L5236]; clearance: The reported clearance when administered orally is 8.79 L/h as observed in pharmacokinetic population studies.[F3283]; _drug_name: Phentermine.", + "drugbank_id: DB14033; indication: Acute, recurrent or chronic urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) due to susceptible organisms (usually Escherichia coli, Klebsiella-Enterobacter, staphylococcus, Proteus mirabilis and, less frequently, Proteus vulgaris) in the absence of obstructive uropathy or foreign bodies [L2804]\n\nMeningococcal meningitis where the organism has been demonstrated to be susceptible. Haemophilus influenzae meningitis as adjunctive therapy with parenteral streptomycin [L2804]\n\nMeningococcal meningitis prophylaxis [L2804].\n\nAcute otitis media due to Haemophilus influenzae when used concomitantly with adequate doses of penicillin or erythromycin (see appropriate labeling for prescribing information) [L2804].\n\nTrachoma, inclusion conjunctivitis, nocardiosis, chancroid, toxoplasmosis as adjunctive therapy with pyrimethamine. Malaria due to chloroquine-resistant strains of Plasmodium falciparum, when used as adjunctive therapy [L2804].\n\nCurrently, the increasing frequency of resistant organisms is a limitation of the usefulness of antibacterial agents including the sulfonamides, especially in the treatment of chronic and recurrent urinary tract infections [L2804].; pharmacodynamics: Sulfisoxazole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with action against most gram-positive and many gram-negative organisms. Many strains of an individual species may be resistant to this drugf. Sulfonamides inhibit the multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus [L2798].; mechanism_of_action: Sulfisoxazole is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid [L2798].; toxicity: LD50=6800 mg/kg (Orally in mice) [L2806].\n\nSulfonamide-induced hypersensitivity reactions, although uncommon, can be severe. They can include rare life-threatening cutaneous reactions such as erythema multiform (Stevens-Johnson syndrome) and toxic epidermal necrolysis. Crystalluria may result in dysuria, renal colic, haematuria and acute renal obstruction [L2803].\n\nOther infrequent reactions include granulocytopenia, agranulocytosis, aplastic anemia, thrombocytopenic purpura and toxic hepatitis. Rarely, hemolysis may occur in individuals deficient in glucose-6-phosphate dehydrogenase [L2803].\n\nThe severe or irreversible adverse effects of sulfisoxazole, which give rise to more complications which may include: nephrotoxicity, blood dyscrasias, interstitial nephritis, hematuria, crystalluria, oliguria, anuria, lumbar pain, and tubular necrosis [L2803].\n\nThe symptomatic adverse reactions produced by sulfisoxazole are more or less tolerable and if severe, may be treated symptomatically, these include anorexia, diarrhea, rashes, pruritus, nausea and vomiting, hypersensitivity reactions, Photosensitivity reactions [L2793].\n\n**Overdosage:** Continuously forced diuresis may be beneficial and an alkaline urine should be initiated [L2793].; metabolism: Sulfisoxazole acetyl is a prodrug of _sulfisoxazole_. The acetyl group is added to make the drug poorly water-soluble and is hydrolyzed in vivo to the active drug [L2804], [L2807].\n\nN1-acetyl sulfisoxazole is metabolized to sulfisoxazole by digestive enzymes in the gastrointestinal tract and is absorbed as sulfisoxazole. This enzymatic splitting is thought to be responsible for slower absorption and lower peak blood concentrations are achieved after administration of an equal oral dose of sulfisoxazole. With sustained administration of acetyl sulfisoxazole, blood concentrations approximate those of sulfisoxazole. Following a single 4 gram dose of acetyl sulfisoxazole to healthy volunteers, maximum plasma concentrations of sulfisoxazole ranged from 122 to 282 mcg/mL (mean, 181 mcg/mL) for the pediatric suspension and occurred between 2 and 6 hours postadministration of sulfisoxazole, in a pharmacokinetic study [L2804].; absorption: Readily absorbed from the gastrointestinal tract [L2793].\n\nIn a pharmacokinetic study, the adjustments for variable renal clearances between oral and intravenous administration and using the unbound plasma concentrations, the bioavailability for an oral dose of sulfisoxazole was found to be 0.95 +/- 0.04 [L2800].; half_life: The serum half-life is 10 -12 hours [L2793].; protein_binding: Approximately 85% of a dose of sulfisoxazole is bound to plasma proteins, primarily to albumin; 65% to 72% of the unbound portion is in the nonacetylated form [L2804].; route_of_elimination: The mean urinary excretion recovery following oral administration of sulfisoxazole is 97% within 48 hours, of which 52% is the parent drug, and the remaining as the N4-acetylated metabolite. It is excreted in human milk [L2793].\n\nSulfisoxazole and its acetylated metabolites are excreted primarily by the kidneys through glomerular filtration [L2804].; volume_of_distribution: The sulfonamides are widely distributed throughout all body tissues [L2793].\n\n It readily crosses the placental barrier and enters into fetal circulation and also crosses the blood-brain barrier. In healthy subjects, cerebrospinal fluid concentrations of sulfisoxazole vary; in patients with meningitis, however, concentrations of free drug in cerebrospinal fluid as high as 94 mcg/mL have been reported [L2804].\n\n\nIn a pharmacokinetic study, the apparent volume of distribution for total drug was 10.9 +/- 2.0 liters and 136 +/- 36 liters for the unbound drug, indicating that sulfisoxazole is primarily distributed extracellularly [L2800].; clearance: The clearance of sulfisoxazole is 18.7 +/- 3.9 ml/min for total drug and 232 +/- 64 ml/min for the unbound drug [L2800].; _drug_name: Acetyl sulfisoxazole.", + "drugbank_id: DB00952; indication: For the acute treatment of migraine attacks with or without aura in adults.; pharmacodynamics: Naratriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonist. Naratriptan has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Naratriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Naratriptan in humans.; mechanism_of_action: Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.; toxicity: Symptoms of overdose include light-headedness, loss of coordination, tension in the neck, and tiredness.; metabolism: Primarily hepatic. In vitro, naratriptan is metabolized by a wide range of cytochrome P450 isoenzymes into a number of inactive metabolites.; absorption: Well absorbed (74% oral biovaility), absorption is rapid with peak plasma concentrations after 2-5 hours. The rate of absorption is slower during a migraine attack.; half_life: 5-8 hours; protein_binding: 28%-31% (over the concentration range of 50 to 1000 ng/mL); volume_of_distribution: * 170 L; clearance: * 6.6 mL/min/kg; _drug_name: Naratriptan.", + "drugbank_id: DB00780; indication: Phenelzine is indicated for the treatment of nonendogenous, neurotic or atypical depression for patients that do not tolerate other forms of therapy.[L1356] \n\nAtypical depression has a high prevalence rate, starts in early life, tends to last longer, is more likely to occur in people with bipolar disorder, has a high comorbidity with anxiety disorder and carries more risk of suicidal behavior. It is important to specify the atypical feature to predict the clinical course of depression and hence generate the best treatment and service. The featuring symptoms of the atypical feature include mood reactivity, two or more of this symptoms: 1) increased appetite, 2) increased sleep, 3) leaden paralysis and 4) interpersonal rejection sensitivity and should not have melancholic or catatonic features of depression.[A31917]\n\nNeurotic depression is a depression of an emotionally unstable person. It is a secondary condition to major personality disorder, neuroses and drug use disorders. Likewise, a primary depression with a family history of depression spectrum disease would fit in this category.[A31922]\n\nA nonendogenous depression is characterized by a disturbance in mood and general outlook. The physical symptoms tend to be less severe and it often occurs in response to stressful life events that keep occurring over a large period of time generating a continuous stress in the daily living.[A31924]; pharmacodynamics: The elimination of monoamine oxidase by phenelzine results in the elevation of brain amines such as 2-phenylethylamine which is a metabolite of phenelzine. These amines have then marked effects on the uptake and release of catecholamines and serotonin in nerve endings.[A31925] Phenelzine is shown to elevate brain levels of the gamma-aminobutyric acid (GABA) and alanine (ALA) as well as to inhibit the activity of the transaminases that normally metabolize these amino acids. In preclinical studies, it has been shown to be neuroprotective in cerebral ischemia.[A15753]; mechanism_of_action: The basic mechanism of action of phenelzine acts as an inhibitor and substrate of monoamine oxidase which subsequently causes an elevation in brain levels of catecholamines and serotonin. It also presents a similar structure to amphetamine which explains the effect on the uptake and release of dopamine, noradrenaline, and serotonin. Phenelzine has been reported to inhibit tyrosine aminotransferase, aromatic amino acid decarboxylase, and dopamine B-hydroxylase.[A31925]; toxicity: Phenelzine, as must of the monoamine oxidase inhibitors, can cause transient, mild and asymptomatic aminotransferase elevations. It has also been reported to be associated with cases of liver injury after 1-3 months of treatment.[A31929]; metabolism: For the metabolic studies, it is assumed that phenelzine is acetylated. Some of the metabolites of phenelzine are phenylacetic acid, 2-phenylethylamine and 4-hydroxyphenylacetic acid as major metabolites and N-acetyl-phenelzine as a minor metabolite.[A31925]; absorption: Phenelzine is rapidly absorbed from the gastrointestinal tract. The decay of the drug action is not dependent on the pharmacokinetic parameters but on the rate of protein synthesis which restores the functional levels of monoamine oxidase.[L1365] The mean Cmax is 19.8 ng/ml and it occurs after 43 minutes of dose administration.[FDA label]; half_life: After administration phenelzine presents a very short half-life of 11.6 hours in humans.[L1365]; protein_binding: Unchanged phenelzine presents a high protein binding which reduced its bioavailability.[T114]; route_of_elimination: The elimination of the administered dose is mainly composed of the phenelzine metabolites, phenylacetic acid and parahydroxyphenylacetic acid that constitute 79% of the dose found in the urine in the first 96 hours.[A31928]; volume_of_distribution: The volume of distribution of phenelzine is hard to determine as drugs from this kind penetrate the CNS very well into the tissue where their activity is desired.[T113]; _drug_name: Phenelzine.", + "drugbank_id: DB06634; indication: Investigated for use/treatment in urinary incontinence and adverse effects (chemotherapy).; _drug_name: Casopitant.", + "drugbank_id: DB09305; indication: Investigated for the treatment of depression.; _drug_name: Aptazapine.", + "drugbank_id: DB06569; indication: Investigated for use/treatment in obesity.; _drug_name: P-57AS3.", + "drugbank_id: DB00320; indication: For the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.; pharmacodynamics: Dihydroergotamine is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. Dihydroergotamine binds with high affinity to 5-HT1Da and 5-HT1Db receptors. It also binds with high affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline a2A, a2B and a receptors, and dopamine D2L and D3 receptors. The therapeutic activity of Dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT1D receptors.; mechanism_of_action: Two theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine: 1) activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache and 2) activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.; toxicity: Side effects include abdominal pain, abnormal speech, coma, confusion, convulsions, hallucinations, increase and/or decrease in blood pressure, nausea, numbness, tingling, pain, and a bluish color of your fingersand toes, slowed breathing, vomiting; metabolism: Hepatic; absorption: Interpatient variable and may be dependent on the administration technique; half_life: 9 hours; protein_binding: 93% (to plasma proteins); route_of_elimination: The major excretory route of dihydroergotamine is via the bile in the feces. \nOnly 6%-7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection.; volume_of_distribution: * 800 L; clearance: * 1.5 L/min; _drug_name: Dihydroergotamine.", + "drugbank_id: DB00490; indication: Indicated for the management of anxiety disorders or the short-term relief of the symptoms of anxiety.[L4478]; pharmacodynamics: The clinical effect of buspirone in alleviating the symptoms of generalized anxiety disorders typically takes 2 to 4 weeks to achieve.[L7375] The delayed onset of action of buspirone suggests that the therapeutic effectiveness in generalized anxiety may involved more than its molecular mechanism of action at the 5-HT1A receptors,[T28] or buspirone may induce adaptations of 5-HT1A receptors.[L7375] Buspirone was not shown to alter the psychomotor or cognitive function in healthy volunteers, and the risk of developing sedation is relatively low compared to other anxiolytics, such as benzodiazepines.[A180985] Unlike benzodiazepines and barbiturates used in anxiety disorders, buspirone is not associated with a risk for developing physical dependence or withdrawal, or any significant interaction with central nervous system depressants such as ethanol. This is due to the lack of effects on GABA receptors.[A180985,L7375] Buspirone also does not exhibit any anticonvulsant or muscle-relaxing properties,[A182309] but may interfere with arousal reactions due to its inhibitory action on the aactivity of noradrenergic locus coerulus neurons.[T28]\n\nDespite its clinical effectiveness in generalized anxiety, buspirone demonstrated limited clinical effectiveness on panic disorders, severe anxiety, phobias, and obsessive compulsive disorders.[A181751,T28] The clinical effectiveness of the long-term use of buspirone, for more than 3 to 4 weeks, has not demonstrated in controlled trials but there were no observable significant adverse events in patients receiving buspirone for a year in a study of long-term use.[L4478]; mechanism_of_action: The therapeutic action of buspirone in generalized anxiety disorders is thought to be mainly derived from its interaction with two major 5-HT1A receptor subtypes that are involved in the brain's anxiety and fear circuitry to enhance the serotonergic activity in these brain areas.[L7375] Buspirone acts as a full agonist at presynaptic 5-HT1A receptors, or 5-HT1A autoreceptors, expressed at dorsal raphe while acting as a partial agonist at the postsynaptic 5-HT1A receptors expressed on hippocampus and cortex.[A182315,A182420] 5-HT1A receptors function as inhibitory autoreceptors by being expressed on the soma or dendrites of serotonergic neurons or mediate postsynaptic actions of 5-HT by being highly expressed on the corticolimbic circuits.[T28] They are inhibitory G-protein coupled receptors that couple to Gi/Go proteins. When activated, presynaptic 5-HT1A autoreceptors causes neuron hyperpolarization and reduces the firing rate of the serotonergic neuron, thereby decreasing extracellular 5-HT levels in the neuron's projection areas. Activated postsynaptic 5-HT1A receptors promote hyperpolarization to released 5-HT on pyramidal neurons.[A182420] \n\nThe anxiolytic action of buspirone is mainly thought to arise from the interaction at presynaptic 5-HT1A autoreceptors. Acting as a potent agonist in these receptors, buspirone initially causes activation of these autoreceptors and inhibition of 5-HT release. It is proposed that buspirone induces desensitization of somatodendritic autoreceptors over time, which may explain the delayed onset of action of the drug. Desensitization of the autoreceptors ultimately results in heightened excitation of serotonergic neurons and enhanced 5-HT release.[T28] Buspirone also displays a weak affinity for serotonin 5HT2 receptors and acts as a weak antagonist on dopamine D2 autoreceptors,[L7375] although there is not much evidence that the action at these receptors contribute to the anxiolytic effect of buspirone.[A182312] It acts as an antagonist at presynaptic dopamine D3 and D4 receptors and may bind to alpha-1 adrenergic receptors as a partial agonist.[A181751]; toxicity: The oral LD50 of buspirone is 196 mg/kg in rat, 655 mg/kg in mouse, 586 mg/kg in dog, and 356 mg/kg in monkey. The intraperitoneal LD50 is 136 mg/kg in rat and 146 mg/kg in mouse.[L4478,L7381] \n\nIn clinical pharmacology trials, administration of buspirone at the dose of 375 mg/day resulted in symptoms of nausea, vomiting, dizziness, drowsiness, miosis, and gastric distress. Few cases of overdosage that have been reported usually resulted in complete recovery. In case of overdose, the use of general symptomatic and supportive treatment is recommended along with immediate gastric lavage and monitoring of respiration, pulse, and blood pressure.[L4478] ; metabolism: Buspirone is extensively metabolized upon administration, where it primarily undergoes hepatic oxidation mediated by the CYP3A4 enzyme. Hydroxylated derivatives are produced, including a pharmacologically active metabolite 1-pyrimidinylpiperazine (1-PP). In animal studies, 1-PP possessed about one quarter of the pharmacological activity of buspirone.[L4478]; absorption: Buspirone is rapidly absorbed following oral administration.[L4478] Bioavailability is low and variable (approximately 5%) due to extensive first pass metabolism. While absorption of buspirone is decreased with concomitant food intake, the first-pass metabolism of the drug is also decreased, resulting in an increased bioavailability [L7375] as well as increased Cmax and AUC.[L4478] Following oral administration of single oral doses of 20 mg, the Cmax ranged from 1 to 6 ng/mL and the Tmax ranged from 40 to 90 minutes.[L4478]; half_life: In a single-dose pharmacokinetic study of 14C-labeled buspirone, the average elimination half-life of unchanged buspirone following administration of single doses ranging from 10 to 40 mg was about 2 to 3 hours.[L4478]; protein_binding: Based on the findings of an _in vitro_ protein binding study, approximately 86% of buspirone is bound to plasma proteins.[L4478] It is mainly bound to serum albumin and alpha-1-acid glycoprotein.[A180991]; route_of_elimination: A single-dose pharmacokinetic studies using 14C-labeled buspirone demonstrated that about 29-63% of the dose administered was excreted in the urine within 24 hours, primarily in the form of metabolites. About 18% to 38% of the dose was eliminated via fecal excretion.[L4478]; volume_of_distribution: In a pharmacokinetic study assessing buspirone over the dose range of 10 to 40 mg, the volume of distribution was 5.3 L/kg.[A181027]; clearance: In a pharmacokinetic study assessing buspirone over the dose range of 10 to 40 mg, the systemic clearance was 1.7 L/h/kg.[A181027]; _drug_name: Buspirone.", + "drugbank_id: DB05417; indication: Investigated for use/treatment in tobacco dependence.; _drug_name: GW 468816.", + "drugbank_id: DB09287; indication: Polyethylene glycol is indicated for use as an over-the-counter osmotic laxative to relieve occasional constipation.[L11812] When used in combination with sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride and potassium chloride, it is used for cleansing of the colon in preparation for colonoscopy in adults.[L6421]; pharmacodynamics: The osmotic effect of PEG produces a copious watery diarrhea. The onset of action of PEG 3350 is about 1 to 2 hours after oral ingestion.[L6421] The colonic transit of polyethylene glycol occurs in a dose-dependent manner.[A190975] When used for bowel preparation before colonscopy, electrolytes are typically added in the oral solution to prevent dehydration and electrolyte disturbances. As an over-the-counter laxative, the OTC product does not contain any salts that can be absorbed.[A177092] In a study involving healthy subjects, PEG 3350 had negligible effects on colonic fluid absorption or with the ability of the colonic mucosa to generate and sustain steep electrochemical gradients.[A190978]; mechanism_of_action: Osmotic laxatives contain substances that are poorly absorbable and draw water into the lumen of the bowel.[L11854] Polyethylene glycol functions is an osmotic laxative that causes increased water retention in the lumen of the colon by binding to water molecules, thereby producing loose stools.[A177092,L6421]; toxicity: The oral LD50 of PEG 3350 in rats is 22000 mg/kg.[L11857]\n\nThere is limited clinical information on the overdose of polyethylene glycols. Based on the pharmacological action of the compound, severe diarrhea may be suspected. Overdose of polyethylene glycols should be responded with symptomatic and supportive care. ; metabolism: Polyethylene glycol is a metabolically inert laxative that does not undergo intestinal enzymatic degradation or bacterial metabolism.[A18713,A177092]; absorption: Following a two-day split-dosing regimen of an oral suspension containing 140 grams of PEG 3350 in healthy subjects, the mean Cmax was 2.7 mcg/mL and the mean Tmax was 3 hours.[L6421] Typically, polyethylene glycols with a high molecular weight are poorly absorbed from the gastrointestinal tract following oral administration.[A190975,A190978]; half_life: Following a two-day split-dosing regimen of an oral suspension containing 140 grams of PEG 3350 in healthy subjects, the mean half life was 4.1 hours.[L6421]; protein_binding: There is limited information on the protein binding profile of polyethylene glycols. ; route_of_elimination: Following administration of an oral suspension containing 140 grams of PEG 3350 in healthy subjects, up to 85% to 99% of the compound was excreted in the feces.[L6421]; volume_of_distribution: Following a two-day split-dosing regimen of an oral suspension containing 140 grams of PEG 3350 in healthy subjects, the mean volume of distribution was 48,481 L.[L6421]; clearance: There is limited information on the clearance rate of polyethylene glycols. ; _drug_name: Polyethylene glycol.", + "drugbank_id: DB04996; indication: Investigated for use/treatment in lung cancer, prostate cancer, and solid tumors.; mechanism_of_action: This drug binds to the DNA of cancer cells, inhibiting cell division.; _drug_name: Satraplatin.", + "drugbank_id: DB06455; indication: Investigated for use/treatment in colorectal cancer, prostate cancer, schizophrenia and schizoaffective disorders, psychosis, depression, and lung cancer.; _drug_name: Meclinertant.", + "drugbank_id: DB04884; indication: For the treatment of premature ejaculation.; pharmacodynamics: Dapoxetine is a selective serotonin reuptake inhibitor currently undergoing trials through Alza (under license from GenuPro, a collaboration between Eli Lilly and PPD). Dapoxetine is a short-acting SSRI drug currently being considered for approval by the Food and Drug Administration (FDA) for the treatment of premature ejaculation in men, which would make it the first drug approved for such treatment. Despite two clinical trials finished in 2006, experts doubt it will be approved by the FDA soon because SSRIs come with undesirable side-effects after long-term use, such as psychiatric problems, dermatological reactions, increase in body weight, lower sex-drive, nausea, headache, upset stomach and weakness, thus not significantly outweighing the benefit of premature ejaculation medication versus the risks. By contrast with SSRIs approved for depression, which take 2 weeks or longer to reach steady-state concentration, dapoxetine has a unique pharmacokinetic profile, with a short time to maximum serum concentration (about 1 h) and rapid elimination (initial half-life of 1-2 h).; mechanism_of_action: The drug's mechanism of action is thought to be related to inhibition of neuronal reuptake of serotonin and subsequent potentiation of serotonin activity. The central ejaculatory neural circuit comprises spinal and cerebral areas that form a highly interconnected network. The sympathetic, parasympathetic, and somatic spinal centers, under the influence of sensory genital and cerebral stimuli integrated and processed at the spinal cord level, act in synergy to command physiologic events occurring during ejaculation. Experimental evidence indicates that serotonin (5-HT), throughout brain descending pathways, exerts an inhibitory role on ejaculation. To date, three 5-HT receptor subtypes (5-HT(1A), 5-HT(1B), and 5-HT(2C)) have been postulated to mediate 5-HT's modulating activity on ejaculation.; absorption: Rapidly absorbed.; half_life: Initial half-life of 1-2 hours.; _drug_name: Dapoxetine.", + "drugbank_id: DB09247; indication: For the treatment of depression.; _drug_name: Iproclozide.", + "drugbank_id: DB09254; indication: For the treatment of depression.; _drug_name: Caroxazone.", + "drugbank_id: DB05585; indication: Investigated for use/treatment in brain cancer, lung cancer, melanoma, and solid tumors.; _drug_name: Verubulin.", + "drugbank_id: DB05670; indication: Investigated for use/treatment in adverse effects (chemotherapy).; _drug_name: ATL-104.", + "drugbank_id: DB12364; indication: Betrixaban is indicated for prophylaxis of venous thromboembolism (VTE) in conditions of moderate to severe restricted mobility or in patients that qualify as in risk of VTE. ; pharmacodynamics: Betrixaban is an oral anticoagulant that excerts its action by preventing thrombin generation without having a direct effect on platelet aggregation [A27288].; mechanism_of_action: Betrixaban is a cofactor-independent direct inhibitor of the Factor Xa and inhibits free and prothrombinase-bound Factor Xa [A7708].; toxicity: Betrixaban presents a minimal hepatotoxicity, which is the main adverse effect found in this class of drugs. Some of the major adverse effects of Betrixaban are bleeding or hypersensitivity [A27287].; metabolism: One of the major characteristics of Betrixaban is its minimal hepatic metabolism (< 1%), preventing potential accumulation with liver impariment. Unchanged Betrixaban is the main form found in human plasma, followed by two hydolitic CYP-independent inactive metabolites (15-18%). The minimal hepatic metabolism produces an unlikely drug-to-drug interaction with inhibitors or agonists of CYP450 [A27287].\n; absorption: Betrixaban presents a rapid absorption at a dose of 80 mg. Its peak plasma concentration is registered within 3-4 hours after oral administration in healthy humans. The oral bioavailability is 34% and it can be reduced with consumption of high fat food [A27287].; half_life: Betrixaban presents a long half-life of between 19-27 hours [A7708].; protein_binding: Betrixaban is reported to be present a proteing binding of about 60% [A27287].; route_of_elimination: Betrixaban is reported to present mainly a gastrointestinal elimination route, it has been shown that even 85% of it gets disposed in the feces and only 11% of it can be found in the urine [A7708]. ; volume_of_distribution: The apparent volume of distribution os 32 L/kg [FDA label].; clearance: Betrixaban presents a minimal renal clearance (being 5-7% of the administered dose) [A27287].; _drug_name: Betrixaban.", + "drugbank_id: DB06660; indication: Investigated for use/treatment in depression and anxiety disorders.; mechanism_of_action: Saredutant works by blocking the effects of Neurokinin A at the NK-2 receptor.; _drug_name: Saredutant.", + "drugbank_id: DB14175; indication: alpha-Amyl cinnamaldehyde is used in allergenic testing.; _drug_name: alpha-Amyl cinnamaldehyde.", + "drugbank_id: DB00953; indication: For treatment of acute migraine attacks with or without aura.; pharmacodynamics: Rizatriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists and has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Rizatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Rizatriptan in humans.; mechanism_of_action: Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.; toxicity: Symptoms of overdose include dizziness, fainting, heart and blood vessel problems, high blood pressure, loss of bowel and bladder control, slow heartbeat, and vomiting.; metabolism: Rizatriptan is metabolized by monoamine oxidase A isoenzyme (MAO-A) to an inactive indole acetic acid metabolite. In addition, several other inactive metabolites are formed. An active metabolite, N-monodesmethyl-rizatriptan, with pharmacological activity similar to that of the parent compound has been identified in small concentrations (14%) in the plasma.; absorption: Rapid following oral administration. Bioavailability is 45%. Food has no effect on the bioavailability of rizatriptan. However, administering rizatriptan with food will delay by 1 hour the time to reach peak plasma concentration. The rate of absorption is not affected by the presence of a migraine attack.; half_life: 2-3 hours; protein_binding: 14%; route_of_elimination: Approximately 14% of an oral dose is excreted in urine as unchanged rizatriptan while 51% is excreted as indole acetic acid metabolite, indicating substantial first pass metabolism.; volume_of_distribution: * 140 L [male]\n* 110 L [female]; _drug_name: Rizatriptan.", + "drugbank_id: DB01079; indication: Tegaserod is a serotonin-4 (5-HT4) receptor agonist indicated for the treatment of adult women less than 65 years of age with irritable bowel syndrome with constipation (IBS-C) [F4223, F4229]. The safety and effectiveness of tegaserod in men with IBS-C have not been established [F4223, F4229].; pharmacodynamics: In general, it has been determined that tegaserod is an agonist of serotonin type-4 (5-HT(4)) receptors, an antagonist at 5-HT(2B) receptors, but is expected to possess minimal binding to 5-HT(1) receptors, and virtually no affinity for 5-HT(3) or dopamine receptors [A11044, A176762, F4223].\n\nIn clinical trials with tegaserod, centrally analyzed ECGs were recorded in 4,605 male and female patients receiving tegaserod 6 mg twice daily or placebo for IBS-C and other related motility disorders [F4223, F4229]. No subject receiving the agent had an absolute QTcF above 480 ms [F4223, F4229]. An increase in QTcF of 30 to 60 ms was observed in 7% of patients receiving tegaserod and 8% receiving placebo [F4223, F4229]. An increase in QTcF of greater than 60 ms was observed in 0.3% and 0.2% of subjects, respectively [F4223, F4229]. The effects of tegaserod on the QTcF interval were ultimately not considered to be clinically meaningful [F4223, F4229].\n\nFurthermore, it was determined that there is a potential for tegaserod and its main metabolite (the M29 metabolite) to increase platelet aggregation in vitro [F4223, F4229]. In one in vitro study, at concentrations up to 10-times the maximum plasma concentration (Cmax) at the recommended dose, tegaserod significantly increased platelet aggregation in a concentration-dependent manner up to 74% (range 11% to 74%) compared to a control vehicle (with potentiation by various agonists) [F4223, F4229]. In another in vitro study, the M29 metabolite, at concentrations up to 0.6-times the Cmax of M29 also showed a 5% to 16% increase in platelet aggregation compared to the control vehicle [F4223, F4229]. The clinical implications of these in vitro platelet aggregation results remain unclear [F4223, F4229].; mechanism_of_action: Irritable bowel syndrome (IBS) is a complex functional disorder comprised of various abnormal and discomforting effects on the gastrointestinal tract and bowel function [A176669, F4223, F4226, F4229]. Although the cause of IBS has yet to be formally elucidated, patient experience has demonstrated that the disorder is typically associated with abdominal pain, abdominal distension, cramping or bloating, variations in urgency for bowel movements, feelings of incomplete evacuation, gastroesophageal reflux, and various other effects [A176669, F4223, F4226, F4229]. In particular, IBS that features constipation as a predominant effect is categorized as constipation-predominant IBS, or IBS-C [F4223, F4229].\n\nConcurrently, 5-Hydroxytryptamine (5-HT, or serotonin) has demonstrated the ability to elicit significant regulatory actions on gastrointestinal motility [A11044]. Specifically, it has been shown that the activation of 5-HT(4) receptors located on motor neurons and interneurons in the gastrointestinal wall can cause the release of acetylcholine, substance P, and calcitonin gene-related peptide that can all facilitate the propulsion of material through the gut [A11044]. Moreover, when 5-HT(4) receptors located in smooth muscle cells are also activated, activities that may alleviate symptoms of IBS-C like esophageal relaxation and the inhibition of human colonic circular muscle contraction can also occur [A11044]. Additionally, activating 5-HT(4) on enteric neurons and enterocytes also cause natural fluid secretion in the gut - an action which also strongly assists in promoting the movement of content along the gastrointestinal tract [A11044].\n\nAlternatively, it has also been observed that 5-HT may participate in generating visceral hyperalgesia in IBS, an observation supported in part by the finding of increased amounts of 5-HT and its metabolites in the plasma of patients experiencing IBS [A176762] It has therefore also been proposed that antagonism of 5-HT(2B) receptors can lead to inhibition of both 5-HT mediated gastrointestinal motility and visceral hypersensitivity [A11044].\n\nSubsequently, because tegaserod is considered to be an agonist of the 5-HT(4) receptor and an antagonist of the 5-HT(2B) receptor at clinically relevant levels, it is believed that tegaserod may elicit its mechanism of action by facilitating activities associated with the activation and antagonism of the 5-HT(4) and 5-HT(2B) receptors, like stimulating peristaltic gastrointestinal reflexes and intestinal secretion, inhibiting visceral sensitivity, enhancing basal motor activity, and normalizing impaired motility throughout the gastrointestinal tract, among other actions [A11044, A176762, F4223, F4226, F4229]. ; toxicity: Single oral doses of 120 mg (which is 20 times the recommended dose) of tegaserod were administered to three healthy subjects in one study [F4223]. All three subjects developed diarrhea and headache. Two of these subjects also reported intermittent abdominal pain and one developed orthostatic hypotension [F4223]. In 28 healthy subjects exposed to 90 to 180 mg per day of tegaserod (which is 7.5 to 15 times the recommended daily dosage) for several days, adverse reactions were diarrhea (100%), headache (57%), abdominal pain (18%), flatulence (18%), nausea (7%), and vomiting (7%) [F4223].\n\nAlthough available data from case reports with tegaserod use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, animal studies involving maternal dietary administration of tegaserod with doses 45 to 71 times the recommended dose demonstrated decreased body weight, delays in developmental landmarks, and decreased survival in rat pups [F4223]. Caution and careful consideration of risks versus benefits are recommended before administering tegaserod to a pregnant woman.\n\nDespite there being little if any data available regarding the presence of tegaserod in human milk, the effects on the breastfed infant, or the effects on milk production, tegaserod and its metabolites are present in rat milk and the milk to plasma concentration ratio is very high in rats [F4223]. Subsequently, because of the potential for serious reactions in the breastfed infant, including tumorigenicity, breastfeeding is not recommended during treatment with tegaserod [F4223].\n\nThe safety and effectiveness of tegaserod in pediatric patients has not yet been established [F4223].\n\nTegaserod is not indicated in patients that are aged 65 years or older [F4223].\n\nTegaserod was not carcinogenic in rats given oral dietary doses up to 180 mg/kg/day (approximately 93 to 111 times the recommended dose based on AUC) for 110 to 124 weeks [F4223]. In mice, dietary administration of tegaserod for 104 weeks produced mucosal hyperplasia and adenocarcinoma of the small intestine at 600 mg/kg/day (approximately 83 to 110 times the recommended dose based on AUC) [F4223]. There was no evidence of carcinogenicity at lower doses (3 to 35 times the recommended dose based on AUC) [F4223]. Tegaserod was not genotoxic in the in vitro Chinese hamster lung fibroblast (CHL/V79) cell chromosomal aberration and forward mutation test, the in vitro rat hepatocyte unscheduled DNA synthesis (UDS) test or the in vivo mouse micronucleus test [F4223]. The results of the Ames test for mutagenicity were equivocal. Tegaserod at oral (dietary) doses up to 240 mg/kg/day (approximately 57 times the recommended dose based on AUC) in male rats and 150 mg/kg/day (approximately 42 times the recommended dose based on AUC) in female rats was found to have no effect on fertility and reproductive performance [F4223].\n\nInhibition of the hERG (human Ether-a-go-go-Related Gene) channel was evident only in the micromolar concentration range with an IC50 of 13 micromolar (approximately 1300 times the Cmax in humans at the recommended dose) [F4223]. In in vitro studies, tegaserod had no effects on impulse conduction in isolated guinea pig papillary muscle at up to 100 times the Cmax in humans, Langendorff-perfused isolated rabbit heart (QT interval) at up to 1000 times the Cmax in humans, or human atrial myocytes at multiples up to 10 times the Cmax in humans [F4223]. The major metabolite, M29, had no effect on QT in the Langendorff-perfused isolated rabbit heart at multiples up to 323 times the Cmax in humans [F4223].\n\nIn anesthetized and conscious dogs, tegaserod at doses up to 92 to 134 times the recommended dose based on Cmax did not alter heart rate, QRS interval duration, QTc or other ECG parameters [F4223]. In chronic toxicology studies in rats and dogs, there were no treatment-related changes in cardiac morphology after tegaserod administration at doses up to 660 times the recommended dose based on AUC [F4223].\n\nAlthough tegaserod is expected to bind to 5-HT2B receptors in humans at the recommended dose, there does not appear to be any potential for heart valve injury based on functional evidence of 5-HT2B receptor antagonism [F4223].\n\nStudies with isolated coronary and mesenteric blood vessels from non-human primates and humans showed no vasoconstrictor effect at concentrations approximately 100 times the human Cmax [F4223]. Tegaserod exhibited antagonism of 5-HT-mediated vasoconstriction via 5-HT1B receptors [F4223]. In rat thoracic aortic rings that were pre-constricted with phenylephrine or norepinephrine, tegaserod produced vasorelaxation, with IC50 values 6 and 64 times the Cmax plasma concentrations in humans, respectively [F4223]. No effects were observed in the basal tone of aortic rings at concentrations up to 1000 times the human Cmax [F4223].\n\nIn studies with an anesthetized rat model for measuring macro- and micro-circulation of the colon, intraduodenal dosing with tegaserod (approximately 7 times the recommended dose based on Cmax) produced no clinically relevant effect on blood pressure, heart rate, or vascular conductance [F4223].; metabolism: Tegaserod is ultimately metabolized by way of hydrolysis and direct glucuronidation [F4223, A38972]. The substance is firstly hydrolyzed in the stomach [F4223, A38972]. It then undergoes oxidization and then conjugation to produce the main circulating tegaserod metabolite in human plasma, the so-called M29 metabolite, or 5-methoxyindole-3-carboxylic acid [F4223, A38972]. Nevertheless, it has been determined that this main circulating metabolite has negligible affinity for 5-HT(4) receptors in vitro [F4223, A38972]. Furthermore, tegaserod can also experience direct N-glucuronidation at each of its three guanidine nitrogens which leads to the generation of three isomeric N-glucuronides - the so-called M43.2, M43.8, and M45.3 metabolites [A38972].; absorption: The absolute bioavailability of tegaserod is approximately 10% when administered to fasting subjects. The median time of peak tegaserod plasma concentration (Tmax) is approximately one hour (range 0.7 to 2 hours) [F4223].\n\nNevertheless, when tegaserod was given to individuals thirty minutes before a meal of high-fat and high-calorie content (about 150 calories from protein, 250 calories from carbohydrates, and 500 calories from fat), the AUC was reduced by 40% to 65%, the Cmax was reduced by approximately 20% to 40%, and the median Tmax was 0.7 hours [F4223]. Additionally, plasma concentrations were similar when tegaserod was administered within thirty minutes before a meal or even two and a half hours after a meal [F4223].; half_life: The mean terminal elimination half-life documented for tegaserod ranges from 4.6 to 8.1 hours following oral administration [F4223].; protein_binding: The protein binding recorded for tegaserod is about 98% [F4223].; route_of_elimination: Approximately two-thirds of an orally administered dose of tegaserod is excreted unchanged in the feces, with the remaining one-third excreted in the urine as metabolites [F4223].; volume_of_distribution: Although tegaserod is not approved for intravenous administration, data regarding the mean volume of distribution of tegaserod at steady-state is recorded as 368 ± 223 L following research of tegaserod administered intravenously [F4223].; clearance: Although tegaserod is not approved for intravenous administration, data regarding the mean plasma clearance of tegaserod is documented as 77 ± 15 L/h following research of tegaserod administered intravenously [F4223].; _drug_name: Tegaserod.", + "drugbank_id: DB05616; indication: Investigated for use/treatment in inflammatory disorders (unspecified), psoriasis and psoriatic disorders, and rheumatoid arthritis.; _drug_name: 4'-Methylene-5,8,10-trideazaaminopterin.", + "drugbank_id: DB06618; indication: Investigated for use/treatment in strokes and depression.; _drug_name: Cutamesine.", + "drugbank_id: DB09246; indication: For the treatment of depression.; _drug_name: Benmoxin.", + "drugbank_id: DB05201; indication: Obesity related disorders such as cardiovascular disease and type II diabetes; mechanism_of_action: About V24343 Scientists have long known that cannabis, which stimulates a receptor in the brain called the CB1 receptor, also stimulates appetite as evidenced by the hunger pangs or \"munchies\" often experienced by cannabis smokers. Blockade of these CB1 receptors by products like V24343 has been shown to cause weight loss and may reduce risk factors for obesity related disorders such as cardiovascular disease and type II diabetes.; _drug_name: V24343.", + "drugbank_id: DB05203; indication: Investigated for use/treatment in hypertension.; _drug_name: SPP1148.", + "drugbank_id: DB06356; indication: Investigated for use/treatment in solid tumors and cancer/tumors (unspecified).; mechanism_of_action: TRC093 (MT293) is a recombinant humanized IgG1 monoclonal antibody that inhibits angiogenesis, tumor cell growth and metastasis by binding cleaved collagen, which is predominantly produced in the extracellular matrix of tumors. TRC093 targets collagen found in the basement membrane of tumor blood vessels. Collagen is a essential triple helix of polypeptide chains found in the extracellular matrix which is involved with many cellular processs including cell proliferation, adhesion, migration, and angiogenesis (neovascularization - growth of new blood vessels). Matrix metalloproteinase enzymes (MMPs) remodel and denature collagen during angiogenesis, causing changes in bioactive sites which results in altered proliferation, adhesion and migration of cells. TRC093 specifically binds to mice breast cancer blood vessel tumors, inhibiting tumor growth. It is proposed that TRC093 binds to hydroxyproline residues of GPO sequences (the major platelet-activating motif within collagen and essential for collagen folding) when they are exposed by thermal denaturation or partially proteolytically degraded by MMPs. TRC093 may target many different types of cancer as a critical component of the TRC093 epitope is a GPOG sequence which are present in high numbers in many different types of collagen. ; _drug_name: TRC093.", + "drugbank_id: DB05750; indication: Investigated for use/treatment in alzheimer's disease, obesity, and schizophrenia and schizoaffective disorders.; mechanism_of_action: AVE-1625 is a selective and potent antagonist of cannabinoid 1 (CB1) receptors having the same mechanism of action as rimonabant.; _drug_name: AVE-1625.", + "drugbank_id: DB04831; indication: For the treatment of hypertension.; _drug_name: Tienilic acid.", + "drugbank_id: DB01556; indication: Used as an appetite suppressant.; pharmacodynamics: Chlorphentermine is a relatively weak stimulant with little abuse potential. It presents a prominent serotonergic profile leading to pulmonary hypertension and cardiac fibrosis after prolonged use. Thus, this drug is no longer used. ; absorption: Well absorbed following oral administration.; half_life: 40 hours; _drug_name: Chlorphentermine.", + "drugbank_id: DB05607; indication: Investigated for use/treatment in chronic obstructive pulmonary disease (COPD) and pulmonary hypertension.; _drug_name: PRX-08066.", + "drugbank_id: DB12548; mechanism_of_action: Sparsentan, which possesses two clinically validated mechanisms of action in a single molecule, works by selectively blocking the action of two potent vasoconstrictor and mitogenic agents, angiotensin II (AII) and endothelin 1 (ET1), at their respective receptors. Sparsentan is highly selective (10,000-fold) for the AII receptor sub-type 1 and the ET receptor sub-type A. As such, Sparsentan combines the properties of an angiotensin receptor blocker (ARB) and an endothelin receptor antagonist (ERA) in the same molecule.; _drug_name: Sparsentan.", + "drugbank_id: DB05562; indication: Investigated for use/treatment in anxiety disorders and depression.; _drug_name: Naluzotan.", + "drugbank_id: DB06604; indication: Investigated for use/treatment in hypertension.; _drug_name: Ilepatril.", + "drugbank_id: DB05012; indication: For the treatment of chronic cancer pain.\n\n; mechanism_of_action: Xen2174 targets the Norepinephrine Transporter (NET). Inhibition of this transporter elevates the levels of norepinephrine (NE) in the spinal cord preventing pain signals from reaching the brain. Xen2174 acts to restore the balance by promoting the activation of inhibitory pain pathways to relieve the sensation of pain.; _drug_name: XEN2174.", + "drugbank_id: DB09253; indication: For the treatment of depression.; _drug_name: Safrazine.", + "drugbank_id: DB08918; indication: Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor and is indicated for the treatment of major depressive disorder (MDD). ; pharmacodynamics: Levomilnacipran binds with high affinity to human serotonin (5-HT) and norepinephrine (NE) transporters (Ki = 11 and 91 nM, respectively). It potently inhibits 5-HT and NE reuptake (IC50 = 16 - 19 and 11 nM, respectively). Levomilnacipran does not bind to any other receptors, ion channels, or transporters, including serotonergic (5HT1-7), α- and β adrenergic, muscarinic, or histaminergic receptors and Ca2+, Na+, K+ or Cl- channels to a significant degree. Levomilnacipran did not inhibit monoamine oxidase (MAO). Furthermore, levomilnacipran does not prolong the QTc interval to a clinically relevant extent. ; mechanism_of_action: The exact mechanism of the antidepressant action of levomilnacipran is unknown but is thought to be related to the potentiation of serotonin and norephinephrine in the central nervous system through inhibition of reuptake at serotonin and norepinephrine transporters. ; toxicity: The most common adverse reactions are nausea, constipation, hyperhidrosis, heart rate increase, erectile dysfunction, tachycardia, vomiting, and palpitations. ; metabolism: Hepatic. Levomilnacipran undergoes desethylation to form desethyl levomilnacipran and hydroxylation to form p-hydroxy-levomilnacipran. Desethylation is facilitated primarily by CYP3A4 and by CYP2C8, 2C19, 2D6, and 2J2 to a lesser extent. Both metabolites undergo further conjugation with glucuronide to form conjugates. ; absorption: The relative bioavailability after administration of the extended-release capsule was 92% when compared to oral solution. Food does not affect the concentration of levomilnacipran. After daily dosing of levomilnacipran (extended-release capsule) the mean Cmax is 341 ng/mL, and the mean steady-state AUC value is 5196 ng·h/mL. The Tmax is 6 - 8 hours after oral administration. Interconversion of stereoisomers does not occur in humans. ; half_life: 12 hours ; protein_binding: 22% bound to human plasma protein over concentration range of 10 to 1000 ng/mL. ; route_of_elimination: Levomilnacipran and its metabolites are eliminated primarily by renal excretion. 58% of the dose is excreted in urine as unchanged levomilnacipran. N-desethyl levomilnacipran is the major metabolite\nexcreted in the urine and accounted for approximately 18% of the dose. Other identifiable metabolites excreted in the urine are levomilnacipran glucuronide (4%), desethyl-levomilnacipran glucuronide (3%), p-hydroxy levomilnacipran glucuronide (1%), and p-hydroxylevomilnacipran (1%). The metabolites are inactive. ; volume_of_distribution: * 387 - 473 L [apparent volume of distribution] ; clearance: * 21 - 29 L/h [mean apparent total clearance] ; _drug_name: Levomilnacipran.", + "drugbank_id: DB09306; indication: Investigated for the treatment of depression.; _drug_name: Metralindole.", + "drugbank_id: DB05095; indication: Investigated for use/treatment in depression.; mechanism_of_action: Depression and schizophrenia are inflammatory diseases. Increased levels of pro-inflammatory cytokines and prostaglandin E (PGE) have repeatedly been described in major depression. COX-2 inhibitors inhibit production of both. Cimicoxib is a selective COX-2 inhibitor. The mechanism by which some COX-2 inhibitors work in depression could be linked to their anti-inflammatory mechanisms.; _drug_name: Cimicoxib.", + "drugbank_id: DB06171; indication: Investigated for use/treatment in brain cancer.; _drug_name: Paclitaxel trevatide.", + "drugbank_id: DB05864; indication: Investigated for use/treatment in lymphoma (non-hodgkin's) and solid tumors.; mechanism_of_action: PPI-2458's potent inhibition of MetAP-2 presents the potential for use as a new therapy for non-Hodgkin's lymphoma (NHL). MetAP-2 is highly expressed in human germinal center B cells. The neoplastic counterparts of these cells are the cell types observed in certain NHL subtypes, such as diffuse large B cell lymphoma and follicular lymphoma. PPI-2458 has been shown to reduce the formation of germinal centers in lymphoid tissues in vivo, have direct anti-proliferative activity on NHL cells in vitro and inhibit the growth of NHL tumors in a preclinical model in vivo. The anti-tumor activity of PPI-2458 was dose-dependent in this preclinical in vivo model and directly correlated with the level of molecular target MetAP-2 enzyme inhibition in tumor tissue, as measured by a proprietary, pharmacodynamic assay developed by PRAECIS. Additionally, the activity of PPI-2458 in this preclinical model was synergistic with several chemotherapeutic agents that are routinely used in combination in NHL patients.; _drug_name: PPI-2458." + ] + }, + { + "example_idx": 3, + "anchor_id": 1262920086908259338, + "positive_id": 10866535609906140090, + "join_paths": [ + [ + 3, + 7, + 0.259765625 + ], + [ + 3, + 27, + 0.2470703125 + ], + [ + 3, + 6, + 0.2138671875 + ], + [ + 3, + 39, + 0.201171875 + ], + [ + 3, + 42, + 0.201171875 + ] + ], + "rows": [ + "The lymphocyte function-associated antigen (LFA-1) belongs to the family of beta2-integrins and plays an important role in T-cell activation and leukocyte migration to sites of inflammation.", + "We report here that lovastatin, a drug clinically used for lowering cholesterol levels, inhibits the interaction of human LFA-1 with its counter-receptor intercellular adhesion molecule-1.", + "Using nuclear magnetic resonance spectroscopy and X-ray crystallography we show that the inhibitor binds to a highly conserved domain of the LFA-1 alpha-chain called the I-domain.", + "The first three-dimensional structure of an integrin inhibitor bound to its receptor reveals atomic details for a hitherto unknown mode of LFA-1 inhibition.", + "It also sheds light into possible mechanisms of LFA-1 mediated signalling and will support the design of novel anti-adhesive and immunosuppressive drugs.", + "Amino Acid Sequence\nBinding Sites\nCD11 Antigens\nCell Adhesion\nCrystallography, X-Ray\nHumans\nIntercellular Adhesion Molecule-1\nLovastatin\nLymphocyte Function-Associated Antigen-1\nMagnetic Resonance Spectroscopy\nModels, Molecular\nMolecular Conformation\nMolecular Sequence Data\nMolecular Structure\nProtein Binding\nProtein Structure, Secondary\nTumor Cells, Cultured" + ], + "sentences": [ + "id: BE0009045; name: Proliferating cell nuclear antigen; organism: Humans; known_action: unknown; position: 12; parent_key: DB00279.", + "id: BE0003496; name: B-lymphocyte antigen CD19; organism: Humans; known_action: yes; position: 1; parent_key: DB13915.", + "id: BE0001085; name: Intercellular adhesion molecule 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB00108.", + "id: BE0004586; name: Catechol O-methyltransferase domain-containing protein 1; organism: Humans; known_action: unknown; parent_key: DB01752.", + "id: BE0001230; name: Cholesterol oxidase; organism: Brevibacterium sterolicum; known_action: unknown; parent_key: DB03147.", + "id: BE0009030; name: Nuclear migration protein nudC; organism: Humans; known_action: unknown; position: 16; parent_key: DB12695.", + "id: BE0000439; name: Integrin alpha-IIb; organism: Humans; known_action: yes; position: 1; parent_key: DB00775.", + "id: BE0000516; name: Integrin alpha-L; organism: Humans; known_action: unknown; position: 13; parent_key: DB01098.", + "id: BE0003066; name: Conserved protein; organism: Mycobacterium tuberculosis; known_action: unknown; parent_key: DB03382.", + "id: BE0003872; name: Disintegrin and metalloproteinase domain-containing protein 28; organism: Humans; known_action: unknown; position: 1; parent_key: DB02255.", + "id: BE0001124; name: Epithelial discoidin domain-containing receptor 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00619.", + "id: BE0003090; name: Focal adhesion kinase 1; organism: Humans; known_action: unknown; position: 272; parent_key: DB12010.", + "id: BE0000917; name: Growth factor receptor-bound protein 2; organism: Humans; known_action: unknown; parent_key: DB03276.", + "id: BE0004501; name: Glycosyltransferase 6 domain-containing protein 1; organism: Humans; known_action: unknown; parent_key: DB04465.", + "id: BE0003774; name: BAG family molecular chaperone regulator 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB07045.", + "id: BE0002446; name: Epithelial cell adhesion molecule; organism: Humans; known_action: unknown; parent_key: DB05831.", + "id: BE0009193; name: Conserved Plasmodium membrane protein; organism: Plasmodium falciparum (isolate 3D7); known_action: unknown; position: 111; parent_key: DB11638.", + "id: BE0000675; name: Anti-Muellerian hormone type-2 receptor; organism: Humans; known_action: unknown; parent_key: DB00171.", + "id: BE0000588; name: Penicillin-binding protein 1A; organism: Escherichia coli (strain K12); known_action: yes; position: 5; parent_key: DB00274.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01239.", + "id: BE0009458; name: Leukocyte tyrosine kinase receptor; organism: Humans; known_action: unknown; position: 170; parent_key: DB12010.", + "id: BE0002203; name: 2-oxoglutarate and iron-dependent oxygenase domain-containing protein 2; organism: Humans; known_action: unknown; position: 15; parent_key: DB00126.", + "id: BE0003314; name: C protein alpha-antigen; organism: Streptococcus agalactiae serotype Ia (strain ATCC 27591 / A909 / CDC SS700); known_action: unknown; parent_key: DB04447.", + "id: BE0004224; name: Carcinoembryonic antigen-related cell adhesion molecule 5; organism: Humans; known_action: unknown; parent_key: DB05097.", + "id: BE0004501; name: Glycosyltransferase 6 domain-containing protein 1; organism: Humans; known_action: unknown; parent_key: DB03685.", + "id: BE0004655; name: Inhibitor of nuclear factor kappa-B kinase subunit alpha; organism: Humans; known_action: unknown; position: 5; parent_key: DB00244.", + "id: BE0001124; name: Epithelial discoidin domain-containing receptor 1; organism: Humans; known_action: unknown; position: 110; parent_key: DB12010.", + "id: BE0000516; name: Integrin alpha-L; organism: Humans; known_action: unknown; parent_key: DB02177.", + "id: BE0004759; name: LIM domain kinase 1; organism: Humans; known_action: unknown; position: 167; parent_key: DB12010.", + "id: BE0004024; name: Lymphocyte antigen 96; organism: Humans; known_action: unknown; position: 39; parent_key: DB08231.", + "id: BE0000433; name: Glycine receptor subunit alpha-1; organism: Humans; known_action: unknown; position: 1; parent_key: DB01956.", + "id: BE0004644; name: Penicillin-binding protein 2a; organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6); known_action: yes; position: 1; parent_key: DB00739.", + "id: BE0003090; name: Focal adhesion kinase 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB07248.", + "id: BE0002446; name: Epithelial cell adhesion molecule; organism: Humans; known_action: unknown; position: 1; parent_key: DB11075.", + "id: BE0000012; name: Voltage-dependent T-type calcium channel subunit alpha-1I; organism: Humans; known_action: yes; position: 14; parent_key: DB00909.", + "id: BE0002404; name: Disintegrin and metalloproteinase domain-containing protein 10; organism: Humans; known_action: unknown; parent_key: DB04991.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 10; parent_key: DB01403.", + "id: BE0004501; name: Glycosyltransferase 6 domain-containing protein 1; organism: Humans; known_action: unknown; parent_key: DB01861.", + "id: BE0003754; name: Disintegrin and metalloproteinase domain-containing protein 17; organism: Humans; known_action: unknown; position: 1; parent_key: DB06943.", + "id: BE0001155; name: Integrin beta-3; organism: Humans; known_action: yes; position: 13; parent_key: DB00451.", + "id: BE0003754; name: Disintegrin and metalloproteinase domain-containing protein 17; organism: Humans; known_action: unknown; position: 1; parent_key: DB07189.", + "id: BE0000085; name: Ferritin light chain; organism: Humans; known_action: unknown; parent_key: DB02285.", + "id: BE0001155; name: Integrin beta-3; organism: Humans; known_action: unknown; position: 4; parent_key: DB15598.", + "id: BE0000721; name: Branched-chain-amino-acid aminotransferase, mitochondrial; organism: Humans; known_action: unknown; parent_key: DB00149.", + "id: BE0003754; name: Disintegrin and metalloproteinase domain-containing protein 17; organism: Humans; known_action: unknown; position: 1; parent_key: DB07079.", + "id: BE0000369; name: Vascular endothelial growth factor receptor 2; organism: Humans; known_action: yes; position: 4; parent_key: DB14840.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00193.", + "id: BE0003872; name: Disintegrin and metalloproteinase domain-containing protein 28; organism: Humans; known_action: unknown; position: 1; parent_key: DB03880.", + "id: BE0003872; name: Disintegrin and metalloproteinase domain-containing protein 28; organism: Humans; known_action: unknown; position: 1; parent_key: DB08733.", + "id: BE0003528; name: Somatostatin receptor type 2; organism: Humans; known_action: yes; position: 2; parent_key: DB09099." + ] + }, + { + "example_idx": 5, + "anchor_id": 13504957426354863574, + "positive_id": 1642071399770550964, + "join_paths": [ + [ + 0, + 14, + 0.29296875 + ], + [ + 0, + 44, + 0.29296875 + ], + [ + 0, + 21, + 0.291015625 + ], + [ + 0, + 38, + 0.2890625 + ], + [ + 0, + 11, + 0.283203125 + ] + ], + "rows": [ + "Atovaquone (also called Mepron, or 566C80) is a napthoquinone used for the treatment of infections caused by pathogens such as Plasmodium spp.", + "and Pneumocystis carinii.", + "The mechanism of action against the malarial parasite is the inhibition of dihydroorotate dehydrogenase (DHOD), a consequence of blocking electron transport by the drug.", + "As an analog of ubiquinone (coenzyme Q [CoQ]), atovaquone irreversibly binds to the mitochondrial cytochrome bc(1) complex; thus, electrons are not able to pass from dehydrogenase enzymes via CoQ to cytochrome c. Since DHOD is a critical enzyme in pyrimidine biosynthesis, and because the parasite cannot scavenge host pyrimidines, the drug is lethal to the organism.", + "Oxygen consumption in P. carinii is inhibited by the drug; thus, electron transport has also been identified as the drug target in P. carinii.", + "However, unlike Plasmodium DHOD, P. carinii DHOD is inhibited only at high atovaquone concentrations, suggesting that the organism may salvage host pyrimidines and that atovaquone exerts its primary effects on ATP biosynthesis.", + "In the present study, the effect of atovaquone on ATP levels in P. carinii was measured directly from 1 to 6 h and then after 24, 48, and 72 h of exposure.", + "The average 50% inhibitory concentration after 24 to 72 h of exposure was 1.5 microgram/ml (4.2 microM).", + "The kinetics of ATP depletion were in contrast to those of another family of naphthoquinone compounds, diospyrin and two of its derivatives.", + "Whereas atovaquone reduced ATP levels within 1 h of exposure, the diospyrins required at least 48 h. After 72 h, the diospyrins were able to decrease ATP levels of P. carinii at nanomolar concentrations.", + "These data indicate that although naphthoquinones inhibit the electron transport chain, the molecular targets in a given organism are likely to be distinct among members of this class of compounds.", + "Adenosine Triphosphate\nAnimals\nAntifungal Agents\nAtovaquone\nDose-Response Relationship, Drug\nMale\nNaphthoquinones\nPentamidine\nPneumocystis\nPneumocystis Infections\nRats\nRats, Inbred BN\nRats, Long-Evans" + ], + "sentences": [ + "name: Mesnex; ingredients: Coenzyme M; parent_key: DB09110.", + "name: Wisderma Most Moist Bio Ampoule; ingredients: Adenosine + Nicotinamide; parent_key: DB02701.", + "name: Pentamidine Isetionate for Injection BP; ingredients: Pentamidine; parent_key: DB00738.", + "name: Mepron; ingredients: Atovaquone; parent_key: DB01117.", + "name: Co-HE-O2-N2 Mixture; ingredients: Carbon monoxide + Helium + Nitrogen + Oxygen; parent_key: DB09152.", + "name: Uromitexan; ingredients: Coenzyme M; parent_key: DB09110.", + "name: Pentamidine Isethionate Inj 300mg/vial BP; ingredients: Pentamidine; parent_key: DB00738.", + "name: Atovaquone and Proguanil Hydrochloride; ingredients: Atovaquone + Proguanil; parent_key: DB01117.", + "name: Oxygen Size D; ingredients: Oxygen; parent_key: DB09140.", + "name: Malarone Pediatric; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Atovaquone and Proguanil Hydrochloride Pediatric; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Atovaquone and Proguanil Hydrochloride Tablets; ingredients: Atovaquone + Proguanil; parent_key: DB01117.", + "name: Smofkabiven; ingredients: Alanine + Arginine + Calcium chloride + Dextrose, unspecified form + Fish oil + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Magnesium sulfate + Medium-chain triglycerides + Methionine + Nitrogen + Olive oil + Phenylalanine + Potassium chloride + Proline + Serine + Sodium acetate + Sodium glycerophosphate + Soybean oil + Taurine + Threonine + Tryptophan + Tyrosine + Valine + Zinc sulfate; parent_key: DB09322.", + "name: Malarone Pediatric; ingredients: Atovaquone + Proguanil; parent_key: DB01117.", + "name: Atovaquone Proguanil; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Oxygen, Refrigerated Liquid; ingredients: Oxygen; parent_key: DB09140.", + "name: Atovaquone and Proguanil HCl; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Atovaquone; ingredients: Atovaquone; parent_key: DB01117.", + "name: Medi Peel Luxury 24k Gold Ampoule; ingredients: Adenosine + Nicotinamide; parent_key: DB02701.", + "name: Pentam 300; ingredients: Pentamidine; parent_key: DB00738.", + "name: Apo-atovaquone; ingredients: Atovaquone; parent_key: DB01117.", + "name: Atovaquone Proguanil; ingredients: Atovaquone + Proguanil; parent_key: DB01117.", + "name: The Oriental Gold BB SPF25 PA 2Plus; ingredients: Adenosine + Arbutin + Titanium dioxide + Zinc oxide; parent_key: DB00640.", + "name: NebuPent; ingredients: Pentamidine; parent_key: DB00738.", + "name: DeNino Diaper Rash; ingredients: Avena sativa flowering top + Lanolin + Medium-chain triglycerides + Zinc oxide; parent_key: DB14253.", + "name: Oxygene - Gas Inh; ingredients: Oxygen; parent_key: DB09140.", + "name: Oxygen Compressed U.S.P.; ingredients: Oxygen; parent_key: DB09140.", + "name: Malarone; ingredients: Atovaquone + Proguanil; parent_key: DB01117.", + "name: Medical Provider Single Use EZ Flu Shot Flucelvax 2014-2015 Kit; ingredients: Influenza A virus A/Brisbane/10/2010 (H1N1) antigen (MDCK cell derived, propiolactone inactivated) + Influenza A virus A/Texas/50/2012 X-223A (H3N2) antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Massachusetts/2/2012 antigen (MDCK cell derived, propiolactone inactivated); parent_key: DB10999.", + "name: Mesna; ingredients: Coenzyme M; parent_key: DB09110.", + "name: Oxygen Helium Mixture 30/70; ingredients: Oxygen; parent_key: DB09140.", + "name: Teva-atovaquone Proguanil; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Mylan-atovaquone/proguanil; ingredients: Atovaquone + Proguanil; parent_key: DB01117.", + "name: Air; ingredients: Oxygen; parent_key: DB09140.", + "name: Oxygen Size E; ingredients: Oxygen; parent_key: DB09140.", + "name: Pentamidine Isethionate; ingredients: Pentamidine; parent_key: DB00738.", + "name: Oxygen; ingredients: Oxygen; parent_key: DB09140.", + "name: Pentacarinat 300 Inj Pws 300mg/vial; ingredients: Pentamidine; parent_key: DB00738.", + "name: Atovaquone and Proguanil Hydrochloride; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Mepron Tab 250mg; ingredients: Atovaquone; parent_key: DB01117.", + "name: Teva-atovaquone Proguanil; ingredients: Atovaquone + Proguanil; parent_key: DB01117.", + "name: Mesna for Injection; ingredients: Coenzyme M; parent_key: DB09110.", + "name: Compressed, N.O.S.; ingredients: Helium + Oxygen; parent_key: DB09155.", + "name: Mylan-atovaquone/proguanil; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Atovaquone and Proguanil Hydrochloride Tablets; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Atovaquone Oral Suspension; ingredients: Atovaquone; parent_key: DB01117.", + "name: Oxygen Size H; ingredients: Oxygen; parent_key: DB09140.", + "name: Super Amazing Revolution For Face; ingredients: Adenosine + Nicotinamide; parent_key: DB00640.", + "name: Malarone; ingredients: Atovaquone + Proguanil; parent_key: DB01131.", + "name: Atovaquone and Proguanil HCl; ingredients: Atovaquone + Proguanil; parent_key: DB01117." + ] + }, + { + "example_idx": 6, + "anchor_id": 8260714623220988021, + "positive_id": 143602409014706550, + "join_paths": [ + [ + 4, + 11, + 0.279296875 + ], + [ + 4, + 24, + 0.2734375 + ], + [ + 4, + 21, + 0.26953125 + ], + [ + 4, + 39, + 0.26953125 + ], + [ + 4, + 44, + 0.26953125 + ] + ], + "rows": [ + "Thymidylate synthase, which is a key enzyme involved in the de novo pathway for pyrimidine nucleotide synthesis, is inhibited by 5-fluorodeoxyuridine monophosphate, forming an inactive ternary complex with intracellular folate.", + "We investigated the effect of a 5-fluorouracil derivative (UFT) with or without low dose leucovorin on the number of 5-fluorodeoxyuridine monophosphate binding sites, thymidine kinase activity and intracellular folate concentration in 1,2-dimethylhydrazine-induced rat colorectal carcinomas.", + "A 10-day administration of UFT with or without leucovorin enhanced the thymidine kinase activity and the number of 5-fluorodeoxyuridine monophosphate binding sites, with an increase of thymidylate synthase mRNA expression.", + "Thymidylate synthase inhibition was slightly increased as the intracellular folate concentration increased.", + "These results indicate that thymidylate synthase inhibition increases when the intracellular folate is exogenously supplemented and maintained at an adequate concentration.", + "1,2-Dimethylhydrazine\nAnimals\nBase Sequence\nBody Weight\nCarcinogens\nColorectal Neoplasms\nDNA Primers\nFluorouracil\nLeucovorin\nOrgan Size\nRNA, Messenger\nRats\nThymidine Kinase\nThymidylate Synthase" + ], + "sentences": [ + "id: BE0001209; name: Casein kinase II subunit alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB08340.", + "id: BE0004499; name: Thymidine kinase; known_action: yes; position: 2; parent_key: DB00194.", + "id: BE0003405; name: Folate receptor alpha; organism: Humans; known_action: unknown; parent_key: DB05168.", + "id: BE0001072; name: Cyclin-dependent kinase 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB08182.", + "id: BE0004145; name: Tyrosine-protein kinase JAK1; organism: Humans; known_action: unknown; position: 2; parent_key: DB04716.", + "id: BE0001016; name: Rho-associated protein kinase 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB13165.", + "id: BE0001501; name: Thymidylate synthase; organism: Lactobacillus casei; known_action: unknown; position: 1; parent_key: DB07511.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03038.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04530.", + "id: BE0001501; name: Thymidylate synthase; organism: Lactobacillus casei; known_action: unknown; parent_key: DB03761.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04696.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: yes; position: 3; parent_key: DB06813.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: unknown; parent_key: DB01643.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02031.", + "id: BE0001501; name: Thymidylate synthase; organism: Lactobacillus casei; known_action: unknown; parent_key: DB03800.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03818.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03541.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02256.", + "id: BE0001501; name: Thymidylate synthase; organism: Lactobacillus casei; known_action: unknown; parent_key: DB01643.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02899.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03800.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: yes; position: 1; parent_key: DB00642.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04457.", + "id: BE0003390; name: Mitogen-activated protein kinase 11; organism: Humans; known_action: unknown; parent_key: DB05157.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: yes; position: 2; parent_key: DB09256.", + "id: BE0003128; name: Thymidylate synthase; organism: Pneumocystis carinii; known_action: unknown; parent_key: DB03800.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04503.", + "id: BE0003841; name: ATP synthase subunit beta, mitochondrial; organism: Humans; known_action: unknown; position: 3; parent_key: DB12695.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: yes; parent_key: DB01101.", + "id: BE0001501; name: Thymidylate synthase; organism: Lactobacillus casei; known_action: unknown; parent_key: DB03798.", + "id: BE0002097; name: Low affinity immunoglobulin gamma Fc region receptor III-A; organism: Humans; known_action: unknown; position: 6; parent_key: DB00002.", + "id: BE0001501; name: Thymidylate synthase; organism: Lactobacillus casei; known_action: unknown; parent_key: DB03541.", + "id: BE0001072; name: Cyclin-dependent kinase 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB07493.", + "id: BE0002212; name: Cyclin-dependent kinase 6; organism: Humans; known_action: yes; position: 7; parent_key: DB12001.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02467.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02223.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: yes; parent_key: DB00544.", + "id: BE0001501; name: Thymidylate synthase; organism: Lactobacillus casei; known_action: unknown; position: 1; parent_key: DB08204.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03274.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: yes; position: 4; parent_key: DB09327.", + "id: BE0000898; name: 5-aminolevulinate synthase, erythroid-specific, mitochondrial; organism: Humans; known_action: unknown; position: 53; parent_key: DB00114.", + "id: BE0003128; name: Thymidylate synthase; organism: Pneumocystis carinii; known_action: unknown; parent_key: DB03541.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: unknown; parent_key: DB05308.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: unknown; position: 2; parent_key: DB03541.", + "id: BE0000324; name: Thymidylate synthase; organism: Humans; known_action: unknown; position: 1; parent_key: DB08478.", + "id: BE0001403; name: Thymidine kinase; known_action: yes; position: 3; parent_key: DB01004.", + "id: BE0001501; name: Thymidylate synthase; organism: Lactobacillus casei; known_action: unknown; position: 1; parent_key: DB06860.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB08131.", + "id: BE0004794; name: Thymidylate synthase 1; organism: Bacillus subtilis (strain 168); known_action: unknown; parent_key: DB03761.", + "id: BE0001438; name: Thymidylate synthase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02752." + ] + }, + { + "example_idx": 7, + "anchor_id": 5974681207138379561, + "positive_id": 2628319764095414859, + "join_paths": [ + [ + 11, + 41, + 0.3203125 + ], + [ + 11, + 19, + 0.31640625 + ], + [ + 7, + 41, + 0.3125 + ], + [ + 6, + 47, + 0.30859375 + ], + [ + 11, + 42, + 0.306640625 + ] + ], + "rows": [ + "Nateglinide (A-4166) is an amino acid derivative with insulinotrophic action in clinical development for treatment of type 2 diabetes.", + "The aim of this study was to determine whether nateglinide's interaction at the K(ATP) channel/sulfonylurea receptor underlies its more rapid onset and shorter duration of action in animal models.", + "Binding studies were carried out with membranes prepared from RIN-m5F cells and HEK-293 cells expressing recombinant human sulfonylurea receptor 1 (SUR1).", + "The relative order for displacement of [(3)H]glibenclamide in competitive binding experiments with RIN-m5F cell membranes was glibenclamide > glimepiride > repaglinide > glipizide > nateglinide > L-nateglinide > tolbutamide.", + "The results with HEK-293/recombinant human SUR1 cells were similar with the exception that glipizide was more potent than repaglinide.", + "Neither nateglinide nor repaglinide had any effect on the dissociation kinetics for [(3)H]glibenclamide, consistent with both compounds competitively binding to the glibenclamide-binding site on SUR1.", + "Finally, the inability to measure [(3)H]nateglinide binding suggests that nateglinide dissociates rapidly from SUR1.", + "Direct interaction of nateglinide with K(ATP) channels in rat pancreatic beta-cells was investigated with the patch-clamp method.", + "The relative potency for inhibition of the K(ATP) channel was repaglinide > glibenclamide > nateglinide.", + "Kinetics of the inhibitory effect on K(ATP) current showed that the onset of inhibition by nateglinide was comparable to glibenclamide but more rapid than that of repaglinide.", + "The time for reversal of channel inhibition by nateglinide was also faster than with glibenclamide and repaglinide.", + "These results suggest that the unique characteristics of nateglinide are largely the result of its interaction at the K(ATP) channel.", + "ATP-Binding Cassette Transporters\nAnimals\nBinding, Competitive\nCarbamates\nCell Membrane\nCell Separation\nCells, Cultured\nCyclohexanes\nGlucose\nGlyburide\nGlycosyltransferases\nHumans\nHypoglycemia\nHypoglycemic Agents\nIn Vitro Techniques\nInsulin\nIslets of Langerhans\nKATP Channels\nKinetics\nMale\nMembrane Proteins\nNateglinide\nPatch-Clamp Techniques\nPhenylalanine\nPiperidines\nPotassium Channel Blockers\nPotassium Channels\nPotassium Channels, Inwardly Rectifying\nRats\nRats, Sprague-Dawley\nRepressor Proteins\nSaccharomyces cerevisiae Proteins\nSulfonylurea Compounds" + ], + "sentences": [ + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Seproxetine.; parent_key: DB06731.", + "drugbank-id: DB00731; name: Nateglinide; description: Butriptyline may decrease the hypoglycemic activities of Nateglinide.; parent_key: DB09016.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Amprenavir.; parent_key: DB00701.", + "drugbank-id: DB00731; name: Nateglinide; description: The therapeutic efficacy of Nateglinide can be decreased when used in combination with Epinephrine.; parent_key: DB00668.", + "drugbank-id: DB00083; name: Botulinum toxin type A; description: The risk or severity of adverse effects can be increased when Flupentixol is combined with Botulinum toxin type A.; parent_key: DB00875.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Cyclosporine can be decreased when combined with Nateglinide.; parent_key: DB00091.", + "drugbank-id: DB00731; name: Nateglinide; description: Quinupramine may decrease the hypoglycemic activities of Nateglinide.; parent_key: DB13246.", + "drugbank-id: DB11090; name: Potassium nitrate; description: Salicylic acid may decrease the excretion rate of Potassium nitrate which could result in a higher serum level.; parent_key: DB00936.", + "drugbank-id: DB01016; name: Glyburide; description: The risk or severity of hypoglycemia can be increased when Gallopamil is combined with Glyburide.; parent_key: DB12923.", + "drugbank-id: DB00731; name: Nateglinide; description: The therapeutic efficacy of Nateglinide can be decreased when used in combination with Teprotumumab.; parent_key: DB06343.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Diacerein.; parent_key: DB11994.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Quinidine can be decreased when combined with Nateglinide.; parent_key: DB00908.", + "drugbank-id: DB00731; name: Nateglinide; description: The therapeutic efficacy of Nateglinide can be decreased when used in combination with Pipotiazine.; parent_key: DB01621.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Cinacalcet.; parent_key: DB01012.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Aprepitant.; parent_key: DB00673.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Amodiaquine.; parent_key: DB00613.", + "drugbank-id: DB00115; name: Cyanocobalamin; description: Cyanocobalamin may decrease the excretion rate of Glipizide which could result in a higher serum level.; parent_key: DB01067.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Levacetylmethadol can be decreased when combined with Nateglinide.; parent_key: DB01227.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Saquinavir.; parent_key: DB01232.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Naloxegol.; parent_key: DB09049.", + "drugbank-id: DB00731; name: Nateglinide; description: The therapeutic efficacy of Nateglinide can be increased when used in combination with Sulfacytine.; parent_key: DB01298.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Hydroxyurea.; parent_key: DB01005.", + "drugbank-id: DB09022; name: Benfluorex; description: Phenelzine may increase the hypoglycemic activities of Benfluorex.; parent_key: DB00780.", + "drugbank-id: DB00731; name: Nateglinide; description: Amphetamine may decrease the excretion rate of Nateglinide which could result in a higher serum level.; parent_key: DB00182.", + "drugbank-id: DB00731; name: Nateglinide; description: The risk or severity of hypoglycemia can be increased when Clinafloxacin is combined with Nateglinide.; parent_key: DB14025.", + "drugbank-id: DB00731; name: Nateglinide; description: The risk or severity of hypoglycemia can be increased when Nateglinide is combined with Rivoglitazone.; parent_key: DB09200.", + "drugbank-id: DB02852; name: Domoic Acid; description: The risk or severity of adverse effects can be increased when Reboxetine is combined with Domoic Acid.; parent_key: DB00234.", + "drugbank-id: DB11107; name: Potassium bitartrate; description: The risk or severity of hyperkalemia can be increased when Potassium bitartrate is combined with Eplerenone.; parent_key: DB00700.", + "drugbank-id: DB11598; name: Antithrombin III human; description: The risk or severity of bleeding can be increased when Eptifibatide is combined with Antithrombin III human.; parent_key: DB00063.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Olodaterol can be decreased when combined with Nateglinide.; parent_key: DB09080.", + "drugbank-id: DB00365; name: Grepafloxacin; description: The metabolism of Grepafloxacin can be decreased when combined with Peginterferon beta-1a.; parent_key: DB09122.", + "drugbank-id: DB00731; name: Nateglinide; description: The risk or severity of hypoglycemia can be increased when Nateglinide is combined with Vildagliptin.; parent_key: DB04876.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Tezacaftor can be decreased when combined with Nateglinide.; parent_key: DB11712.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Clonidine.; parent_key: DB00575.", + "drugbank-id: DB00731; name: Nateglinide; description: The therapeutic efficacy of Nateglinide can be decreased when used in combination with Lopinavir.; parent_key: DB01601.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Indisulam.; parent_key: DB06370.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Tienilic acid.; parent_key: DB04831.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Istradefylline can be decreased when combined with Nateglinide.; parent_key: DB11757.", + "drugbank-id: DB00588; name: Fluticasone propionate; description: The therapeutic efficacy of Varicella Zoster Vaccine (Recombinant) can be decreased when used in combination with Fluticasone propionate.; parent_key: DB13924.", + "drugbank-id: DB00731; name: Nateglinide; description: The risk or severity of hypoglycemia can be increased when Nateglinide is combined with Lixisenatide.; parent_key: DB09265.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Apomorphine.; parent_key: DB00714.", + "drugbank-id: DB00731; name: Nateglinide; description: Nateglinide may decrease the excretion rate of Potassium chloride which could result in a higher serum level.; parent_key: DB00761.", + "drugbank-id: DB00731; name: Nateglinide; description: Salicylic acid may increase the hypoglycemic activities of Nateglinide.; parent_key: DB00936.", + "drugbank-id: DB00731; name: Nateglinide; description: The therapeutic efficacy of Nateglinide can be increased when used in combination with Ciprofloxacin.; parent_key: DB00537.", + "drugbank-id: DB00731; name: Nateglinide; description: The excretion of Stavudine can be decreased when combined with Nateglinide.; parent_key: DB00649.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Belinostat.; parent_key: DB05015.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Ivacaftor can be decreased when combined with Nateglinide.; parent_key: DB08820.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Sulfinpyrazone.; parent_key: DB01138.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Cyclizine.; parent_key: DB01176.", + "drugbank-id: DB00731; name: Nateglinide; description: The metabolism of Nateglinide can be decreased when combined with Melperone.; parent_key: DB09224." + ] + }, + { + "example_idx": 8, + "anchor_id": 1079238650411603491, + "positive_id": 10894928961604365626, + "join_paths": [ + [ + 22, + 5, + 0.267578125 + ], + [ + 22, + 7, + 0.26171875 + ], + [ + 22, + 27, + 0.25390625 + ], + [ + 6, + 5, + 0.2314453125 + ], + [ + 8, + 5, + 0.2314453125 + ] + ], + "rows": [ + "1.", + "The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera.", + "5-HT released from enterochromaffin cells after cholera toxin exposure is thought to activate non-neuronally (5-HT(2) dependent) and neuronally (5-HT(3) dependent) mediated water and electrolyte secretion.", + "CT-secretion can be reduced by preventing the release of 5-HT.", + "Enterochromaffin cells possess numerous receptors that, under basal conditions, modulate 5-HT release.", + "2.", + "These include basolateral 5-HT(3) receptors, the activation of which is known to enhance 5-HT release.", + "3.", + "Until now, 5-HT(3) receptor antagonists (e.g.", + "granisetron) have been thought to inhibit cholera toxin-induced fluid secretion by blockading 5-HT(3) receptors on secretory enteric neurones.", + "Instead we postulated that they act by inhibiting cholera toxin-induced enterochromaffin cell degranulation.", + "4.", + "Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 microg kg(-1), lidoocaine 6 mg kg(-1) or saline, were instilled with a supramaximal dose of cholera toxin or saline.", + "Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection.", + "5.", + "Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity.", + "6.", + "Both lidocaine and granisetron inhibited fluid secretion.", + "However, granisetron alone, and proportionately, reduced 5-HT release.", + "7.", + "The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT(3) receptors.", + "The accentuated 5-HT release promotes cholera toxin-induced fluid secretion.", + "Animals\nCholera Toxin\nElectrolytes\nGranisetron\nIntestinal Mucosa\nIntestines\nLidocaine\nMale\nRats\nRats, Wistar\nReceptors, Serotonin\nReceptors, Serotonin, 5-HT3\nSerotonin\nSerotonin Antagonists" + ], + "sentences": [ + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 2; parent_key: DB01151.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB06204.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB00715.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 3; parent_key: DB00579.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB00215.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB13025.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 1; parent_key: DB00289.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB11273.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB06684.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB13946.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 6; parent_key: DB09195.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 9; parent_key: DB08604.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 16; parent_key: DB00543.", + "id: BE0000045; name: Muscarinic acetylcholine receptor M3; organism: Humans; known_action: unknown; position: 3; parent_key: DB00809.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB00472.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB01175.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; parent_key: DB04896.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 6; parent_key: DB08918.", + "id: BE0003383; name: Growth hormone secretagogue receptor type 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB13074.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB09016.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB06148.", + "id: BE0000148; name: NAD-dependent malic enzyme, mitochondrial; organism: Humans; known_action: unknown; parent_key: DB03589.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; parent_key: DB01454.", + "id: BE0002159; name: Glutamate decarboxylase 2 (Pancreatic islets and brain, 65kDa); organism: Humans; known_action: unknown; position: 44; parent_key: DB00114.", + "id: BE0001326; name: Ferrichrome-iron receptor; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03017.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 29; parent_key: DB00408.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 11; parent_key: DB01363.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: no; position: 4; parent_key: DB12141.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; parent_key: DB06156.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; parent_key: DB04836.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 3; parent_key: DB06700.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 5; parent_key: DB00852.", + "id: BE0000852; name: Platelet-derived growth factor receptor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB00102.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 2; parent_key: DB00540.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 12; parent_key: DB00454.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 2; parent_key: DB00321.", + "id: BE0000705; name: Cysteinyl leukotriene receptor 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB08855.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB00458.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 1; parent_key: DB01114.", + "id: BE0003383; name: Growth hormone secretagogue receptor type 1; organism: Humans; known_action: unknown; parent_key: DB12128.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00967.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; parent_key: DB00726.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 3; parent_key: DB06701.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB04821.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB00988.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; parent_key: DB05688.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB01242.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 12; parent_key: DB00182.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 2; parent_key: DB06077.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; parent_key: DB04832." + ] + }, + { + "example_idx": 9, + "anchor_id": 2974409159297512266, + "positive_id": 8568137007813382143, + "join_paths": [ + [ + 12, + 11, + 0.28515625 + ], + [ + 12, + 21, + 0.28515625 + ], + [ + 12, + 10, + 0.283203125 + ], + [ + 12, + 13, + 0.283203125 + ], + [ + 12, + 33, + 0.283203125 + ] + ], + "rows": [ + "Gulf War veterans were taking pyridostigmine orally against possible exposure to nerve agents as well as being under physical stress.", + "This study was designed to investigate the delayed effects of pyridostigmine and treadmill exercise on cholinesterase activity, lipid peroxidation and histology of peripheral tissues of mice.", + "Male NIH Swiss mice were divided into four groups of 15 animals each and treated as follows: sedentary control; exercise training for 10 weeks; pyridostigmine (1.2 mg kg(-1), p.o.)", + "for 2 weeks during weeks 5 and 6; and pyridostigmine plus exercise training.", + "The mice were sacrificed 24 h after the last exercise, and blood, triceps muscle and sciatic nerve were isolated and analyzed.", + "The group treated with pyridostigmine alone showed decreased plasma butyrylcholinesterase (BChE) activity (87% of control), whereas pyridostigmine plus exercise significantly decreased the BChE activity (79% of control), indicating an interactive effect of the combination.", + "Acetylcholinesterase (AChE) activity did not alter significantly in red blood cells, platelets or sciatic nerve with either of the treatments.", + "However, AChE activity in triceps muscle decreased significantly (78% of control) in the group treated with pyridostigmine plus exercise.", + "Creatine phosphokinase activity in plasma increased slightly (compared to control, pyridostigmine or exercise group) in mice treated with pyridostigmine plus exercise, which may be indicative of perturbation in the integrity of the skeletal muscle due to combination.", + "However, there were no obvious histological abnormalities in the triceps muscle detected between experimental and control groups.", + "Interaction of pyridostigmine and exercise significantly increased the concentration of the end product of lipid peroxidation (malondialdehyde) (124% of control) in triceps muscle, indicating an oxidative stress response of the combination.", + "These results indicate that physical stress enhanced the delayed toxic effects of a subchronic oral dose of pyridostigmine primarily in the skeletal muscle of mice.", + "Acetylcholinesterase\nAnimals\nButyrylcholinesterase\nCholinesterase Inhibitors\nCreatine Kinase\nDelayed-Action Preparations\nLipid Peroxidation\nMale\nMice\nMuscles\nPhysical Conditioning, Animal\nPyridostigmine Bromide\nStress, Physiological" + ], + "sentences": [ + "id: BE0002440; name: Plasma kallikrein; organism: Humans; known_action: unknown; position: 96; parent_key: DB14487.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB03005.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00239.", + "id: BE0009383; name: Serine/threonine-protein kinase 24; organism: Humans; known_action: unknown; position: 22; parent_key: DB12010.", + "id: BE0009491; name: Muscle, skeletal receptor tyrosine-protein kinase; organism: Humans; known_action: unknown; position: 213; parent_key: DB12010.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; parent_key: DB00545.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB02673.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 1; parent_key: DB02404.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB00122.", + "id: BE0003699; name: Matrix metalloproteinase-24; organism: Humans; known_action: yes; position: 19; parent_key: DB00786.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; position: 1; parent_key: DB00733.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; parent_key: DB01122.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB02166.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 2; parent_key: DB02343.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; position: 1; parent_key: DB00677.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; parent_key: DB00944.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 5; parent_key: DB00449.", + "id: BE0009373; name: Skin epithelial cells; organism: Humans; known_action: yes; position: 2; parent_key: DB12328.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; parent_key: DB01010.", + "id: BE0002216; name: Cyclin-dependent kinase 4; organism: Humans; known_action: yes; position: 1; parent_key: DB11730.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB03359.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; parent_key: DB00981.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 1; parent_key: DB04114.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 2; parent_key: DB02845.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 5; parent_key: DB00863.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; parent_key: DB00989.", + "id: BE0000860; name: Receptor activity-modifying protein 2; organism: Humans; known_action: yes; position: 3; parent_key: DB01278.", + "id: BE0009496; name: Serine/threonine-protein kinase Nek1; organism: Humans; known_action: unknown; position: 219; parent_key: DB12010.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; parent_key: DB00382.", + "id: BE0009370; name: Thiol groups; organism: Humans; known_action: yes; position: 1; parent_key: DB13960.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; position: 1; parent_key: DB00843.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; position: 1; parent_key: DB00674.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB02226.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 2; parent_key: DB00411.", + "id: BE0000861; name: Receptor activity-modifying protein 3; organism: Humans; known_action: yes; position: 4; parent_key: DB01278.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB02825.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 3; parent_key: DB01199.", + "id: BE0002112; name: Plasma serine protease inhibitor; organism: Humans; known_action: unknown; parent_key: DB05413.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB01245.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB03128.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB01805.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; position: 5; parent_key: DB00805.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; parent_key: DB01400.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB03348.", + "id: BE0003106; name: Nucleoside diphosphate kinase A; organism: Humans; known_action: unknown; position: 7; parent_key: DB01593.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB01161.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: yes; position: 2; parent_key: DB00483.", + "id: BE0004064; name: MAP kinase-activated protein kinase 3; organism: Humans; known_action: unknown; position: 2; parent_key: DB08358.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; parent_key: DB03283.", + "id: BE0000859; name: Receptor activity-modifying protein 1; organism: Humans; known_action: yes; position: 2; parent_key: DB01278." + ] + }, + { + "example_idx": 10, + "anchor_id": 10318293019689524941, + "positive_id": 459989070365788214, + "join_paths": [ + [ + 6, + 24, + 0.2333984375 + ], + [ + 6, + 47, + 0.2333984375 + ], + [ + 6, + 38, + 0.232421875 + ], + [ + 6, + 31, + 0.2314453125 + ], + [ + 6, + 35, + 0.2314453125 + ] + ], + "rows": [ + "PURPOSE: The objective of this investigation was to determine the influence of pre-treatment with the irreversible mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA) on the pharmacokinetic-pharmacodynamic (PK/PD) relationship of alfentanil in rats.", + "METHODS: The PK/PD correlation of alfentanil (2 mg x kg(-1) intravenously in 20 min) was determined in chronically instrumented rats using amplitudes in the 0.5-4.5 Hz frequency band of the EEG as pharmacodynamic endpoint.", + "Beta-FNA was administered intravenously (10 mg x kg(-1)) either 35 min or 24 h prior to the PK/PD experiments.", + "RESULTS: Pre-treatment with beta-FNA had no influence on the pharmacokinetics of alfentanil.", + "The in vivo concentration-EEG effect relationships, however, were steeper and shifted towards higher concentrations with no difference between the 35-min and the 24-h pre-treatment groups.", + "Analysis of the data on basis of the operational model agonism revealed that the observed changes could be explained by a 70-80% reduction in alfentanil efficacy in beta-FNA pre-treated rats.", + "This is consistent with results from an in vitro receptor bioassay showing a 40-60% reduction in the number of specific mu-opioid binding sites in the brain.", + "CONCLUSIONS: This investigation confirms the validity of a previously postulated mechanism-based PK/PD model for the effect of synthetic opiates in rats.", + "Alfentanil\nAnalgesics, Opioid\nAnimals\nElectroencephalography\nMale\nNaltrexone\nNarcotic Antagonists\nRadioligand Assay\nRats\nRats, Wistar\nReceptors, Opioid, mu" + ], + "sentences": [ + "id: BE0000420; name: Delta-type opioid receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB00295.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB01439.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00647.", + "id: BE0003872; name: Disintegrin and metalloproteinase domain-containing protein 28; organism: Humans; known_action: unknown; parent_key: DB03088.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB01565.", + "id: BE0000067; name: Nitric oxide synthase, brain; organism: Humans; known_action: unknown; parent_key: DB02143.", + "id: BE0000420; name: Delta-type opioid receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00854.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00193.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; parent_key: DB06409.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB01209.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00333.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: unknown; parent_key: DB06409.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: unknown; position: 1; parent_key: DB13983.", + "id: BE0000420; name: Delta-type opioid receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB01192.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB01081.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB01183.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00956.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB02932.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; parent_key: DB05509.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: unknown; position: 38; parent_key: DB01238.", + "id: BE0001122; name: Transient receptor potential cation channel subfamily A member 1; organism: Humans; known_action: yes; position: 3; parent_key: DB14050.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB01535.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00652.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB00327.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 9; parent_key: DB01221.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB01571.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB12662.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB14146.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: no; position: 2; parent_key: DB06800.", + "id: BE0005562; name: G-protein coupled receptor 35; organism: Humans; known_action: unknown; position: 1; parent_key: DB11156.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 8; parent_key: DB06738.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB06800.", + "id: BE0004735; name: Interleukin-1 receptor antagonist protein; organism: Humans; known_action: unknown; position: 3; parent_key: DB06372.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB08020.", + "id: BE0000501; name: Alpha-1A adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00449.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB09289.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00647.", + "id: BE0000420; name: Delta-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00704.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB00904.", + "id: BE0001778; name: Beta-lactamase OXA-2; organism: Salmonella typhimurium; known_action: unknown; parent_key: DB03801.", + "id: BE0005562; name: G-protein coupled receptor 35; organism: Humans; known_action: unknown; position: 12; parent_key: DB00695.", + "id: BE0000478; name: Gamma-aminobutyric acid receptor subunit alpha-4; organism: Humans; known_action: yes; position: 4; parent_key: DB01496.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00844.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; parent_key: DB05046.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00844.", + "id: BE0000420; name: Delta-type opioid receptor; organism: Humans; known_action: unknown; position: 40; parent_key: DB01238.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00318.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 25; parent_key: DB14009.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB11130.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00295." + ] + }, + { + "example_idx": 11, + "anchor_id": 10000911363814063683, + "positive_id": 9027890862940132109, + "join_paths": [ + [ + 6, + 30, + 0.1806640625 + ], + [ + 6, + 9, + 0.171875 + ], + [ + 6, + 5, + 0.1611328125 + ], + [ + 6, + 41, + 0.1611328125 + ], + [ + 6, + 23, + 0.16015625 + ] + ], + "rows": [ + "Grepafloxacin and levofloxacin transport by Caco-2 cell monolayers was examined to characterize the intestinal behavior of these quinolones.", + "The levels of transcellular transport of [(14)C]grepafloxacin and [(14)C]levofloxacin from the basolateral to the apical side were greater than those in the opposite direction.", + "The unidirectional transport was inhibited by the presence of excess unlabeled quinolones, accompanied by increased accumulation.", + "The inhibitory effects of cyclosporin A plus grepafloxacin on basolateral-to-apical transcellular transport and cellular accumulation of [(14)C]grepafloxacin were comparable to those of cyclosporin A alone, indicating that the transport of grepafloxacin across the apical membrane was mainly mediated by P-glycoprotein.", + "On the other hand, basolateral-to-apical transcellular transport of [(14)C]levofloxacin in the presence of cyclosporin A was decreased by unlabeled levofloxacin, grepafloxacin, and enoxacin, accompanied by significantly increased cellular accumulation.", + "The organic cation cimetidine, organic anion p-aminohippurate, and the multidrug resistance-related protein (MRP) modulator probenecid did not affect the transcellular transport of [(14)C]grepafloxacin or [(14)C]levofloxacin in the presence of cyclosporin A.", + "The basolateral-to-apical transcellular transport of levofloxacin in the presence of cyclosporin A showed concentration-dependent saturation with an apparent Michaelis constant of 5.6 mM.", + "In conclusion, these results suggested that basolateral-to-apical flux of quinolones was mediated by P-glycoprotein and a specific transport system distinct from organic cation and anion transporters and MRP.", + "Anti-Infective Agents\nBiological Transport\nCaco-2 Cells\nCyclosporine\nDose-Response Relationship, Drug\nFluoroquinolones\nHumans\nIntestinal Mucosa\nLevofloxacin\nMetabolic Clearance Rate\nOfloxacin\nPiperazines" + ], + "sentences": [ + "name: Levaquin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Levaquin 25mg/ml; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Auro-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Riva-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Novo-ofloxacin; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Levofloxacin In 5% Dextrose Injection; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Neoral 100mg; ingredients: Cyclosporine; parent_key: DB00091.", + "name: Levaquin 750mg; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Floxin Tablets 200mg; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Dom-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Ava-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Quinsair; ingredients: Levofloxacin; parent_key: DB01137.", + "name: PMS-ofloxacin; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Yellow Jacket hymenoptera venom Venomil Diagnostic; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11031.", + "name: Floxin Otic; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Benuryl; ingredients: Probenecid; parent_key: DB01032.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB04815.", + "name: Ofloxacin; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Ofloxacin Otic; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Neoral; ingredients: Cyclosporine; parent_key: DB00091.", + "name: Hemorro-dol Sup; ingredients: Balsam of Peru + Belladonna + Benzocaine + Bismuth subcarbonate + Bismuth subnitrate + Boric acid + Ephedrine + Zinc oxide; parent_key: DB09321.", + "name: Ocuflox; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Probenecid; ingredients: Probenecid; parent_key: DB01032.", + "name: Mylan-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Tagamet Liquid 60mg/ml; ingredients: Cimetidine; parent_key: DB00501.", + "name: Raxar; ingredients: Grepafloxacin; parent_key: DB00365.", + "name: Levofloxacin Injection; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Yellow Jacket hymenoptera venom Multidose; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11031.", + "name: Iquix; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Act Levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Teva-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Ofloxacin Tablets; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Levaquin 500mg; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Floxin Tablets 400mg; ingredients: Ofloxacin; parent_key: DB01165.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14180.", + "name: Apo-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Floxin; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Floxin I.V. Liq 20mg/ml; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Orajel 3X Medicated For Toothache and Gum; ingredients: Benzocaine + Levomenthol + Zinc cation; parent_key: DB14532.", + "name: Ntp-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: PHL-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Levaquin 5mg/ml; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Benemid Tab 500mg; ingredients: Probenecid; parent_key: DB01032.", + "name: Ofloxacin ophthalmic; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Floxin Tablets 300mg; ingredients: Ofloxacin; parent_key: DB01165.", + "name: Sandoz Levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: PMS-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14178.", + "name: Quixin; ingredients: Levofloxacin; parent_key: DB01137." + ] + }, + { + "example_idx": 12, + "anchor_id": 1762730860981903707, + "positive_id": 5900243029679177735, + "join_paths": [ + [ + 2, + 32, + 0.34765625 + ], + [ + 2, + 37, + 0.33203125 + ], + [ + 2, + 28, + 0.3203125 + ], + [ + 2, + 13, + 0.30859375 + ], + [ + 8, + 32, + 0.306640625 + ] + ], + "rows": [ + "Nicotine has long been known to interact with nicotinic acetylcholine (ACh) receptors since Langley used it extensively to chart sympathetic ganglia a century ago.", + "It has also been used as an effective insecticide.", + "However, it was not until the 1990s that the significance of nicotine was increasingly recognized from the toxicological, pharmacological, and environmental points of view.", + "This is partly because studies of neuronal nicotinic ACh receptors are rapidly emerging from orphan status, fueled by several lines of research.", + "Since Alzheimer's disease is known to be associated with down-regulation of cholinergic activity in the brain, a variety of nicotine derivatives are being tested and developed for treatment of the disease.", + "Public awareness of the adverse effects of nicotine has reached the highest level recently.", + "Since insect resistance to insecticides is one of the most serious issues in the pest-control arena, it is an urgent requirement to develop new insecticides that act on target sites not shared by the existing insecticides.", + "The neuronal nicotinic ACh receptor is one of them, and new nicotinoids are being developed.", + "Thus, the time is ripe to discuss the mechanism of action of nicotine from a variety of angles, including the molecular, physiological, and behavioral points of view.", + "This Symposium covered a wide area of nicotine studies: genetic, genomic, and functional aspects of nicotinic ACh receptors were studied, as related to anthelmintics and insecticides; interactions between ethanol and nicotine out the ACh receptor were analyzed, in an attempt to explain the well-known heavy drinker-heavy smoker correlation; the mechanisms that underlie the desensitization of ACh receptors were studied as related to nicotine action; selective pharmacological profiles of nicotine, and descriptions of some derivatives were described; and chronic nicotine infusion effects on memory were examined using animal models.", + "Animals\nAnthelmintics\nDose-Response Relationship, Drug\nDrug Interactions\nEthanol\nHippocampus\nHumans\nInsecticides\nMemory\nNeurons\nNicotine\nReceptors, Nicotinic\nUp-Regulation" + ], + "sentences": [ + "name: Sound Body Nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotine Polacrilex coated fruit; ingredients: Nicotine; parent_key: DB00184.", + "name: Habitrol Combination Kit STEPS 1-3 TRANSDERMAL SYSTEM; ingredients: Nicotine + Nicotine + Nicotine; parent_key: DB00184.", + "name: Nicotine Polacrilex coated mint; ingredients: Nicotine; parent_key: DB00184.", + "name: Leader Nicotine Transdermal System Step 1; ingredients: Nicotine; parent_key: DB00184.", + "name: DG Health nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicorette Original; ingredients: Nicotine; parent_key: DB00184.", + "name: Leader Nicotine Transdermal System Step 3; ingredients: Nicotine; parent_key: DB00184.", + "name: Habitrol Step 3; ingredients: Nicotine; parent_key: DB00184.", + "name: Hand Sanitizer Vitamin E; ingredients: Ethanol; parent_key: DB00898.", + "name: Zonnic Nicotine Polacrilex; ingredients: Nicotine; parent_key: DB00184.", + "name: Leader Nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: NICOTINE Transdermal System Step 2; ingredients: Nicotine; parent_key: DB00184.", + "name: Basic Care Nicotine; ingredients: Nicotine + Nicotine; parent_key: DB00184.", + "name: Nicotine Polacrilex MINT; ingredients: Nicotine; parent_key: DB00184.", + "name: In Control Nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: 4248 First Aid Kit; ingredients: Acetaminophen + Acetaminophen + Acetylsalicylic acid + Ammonia + Bacitracin + Benzalkonium + Benzethonium + Benzethonium + Benzocaine + Benzocaine + Caffeine + Calcium carbonate + Ethanol + Hydrocortisone acetate + Hydrocortisone acetate + Isopropyl alcohol + Levomenthol + Lidocaine + Neomycin + Phenylephrine + Polymyxin B + Salicylamide + Tetryzoline + Water; parent_key: DB00626.", + "name: Nicorette Cinnamon Surge; ingredients: Nicotine; parent_key: DB00184.", + "name: Signature Care Nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicorette Fruit Chill; ingredients: Nicotine; parent_key: DB00184.", + "name: Anti-Bacterial Hand Sanitizer Days Until Summer; ingredients: Ethanol; parent_key: DB00898.", + "name: Topcare Nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicorette White Mint nicotine polacrilex; ingredients: Nicotine; parent_key: DB00184.", + "name: 4133 First Aid Kit; ingredients: Ammonia + Ethanol + Isopropyl alcohol + Lidocaine + Lidocaine + Povidone-iodine + Water; parent_key: DB00281.", + "name: Equaline Nicotine Transdermal System Step 1; ingredients: Nicotine; parent_key: DB00184.", + "name: Topcare nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: Anti-Bacterial Hand Vanilla Sprinkle Cookie; ingredients: Ethanol; parent_key: DB00898.", + "name: Nicorette Fresh Mint; ingredients: Nicotine; parent_key: DB00184.", + "name: Berkley and Jensen Nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotine Polacrilex coated cinnamon; ingredients: Nicotine; parent_key: DB00184.", + "name: Habitrol Patch Nicotine Transdermal System, Step 3; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotine Transdermal System Step 3; ingredients: Nicotine; parent_key: DB00184.", + "name: Berkley and Jensen NICOTINE; ingredients: Nicotine; parent_key: DB00184.", + "name: 4336 First Aid Kit; ingredients: Bacitracin + Benzalkonium + Ethanol + Lidocaine + Lidocaine + Neomycin + Polymyxin B + Povidone-iodine + Water; parent_key: DB00898.", + "name: Antimicrobial Hand Sanitizer Gel - Fresh; ingredients: Ethanol; parent_key: DB00898.", + "name: Nicorette Cinnamon Surge nicotine polacrilex; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotac Nicotine Polacrilex Coated Mint; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotine UN1654; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotine Polacrilex Coated Mint; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotine Polacrilex Stop Smoking Aid; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotine Transdermal System; ingredients: Nicotine + Nicotine + Nicotine; parent_key: DB00184.", + "name: Maxi Nicotine; ingredients: Nicotine; parent_key: DB00184.", + "name: Nicotine Polacrilex coated ice mint; ingredients: Nicotine; parent_key: DB00184.", + "name: Alcohol Wipes; ingredients: Ethanol; parent_key: DB00898.", + "name: Habitrol Step 2; ingredients: Nicotine; parent_key: DB00184.", + "name: PatchFetch CLEAN-K PERFECTION HAND SANITIZER; ingredients: Ethanol; parent_key: DB00898.", + "name: Safeway Nicotine Transdermal System Step 3; ingredients: Nicotine; parent_key: DB00184.", + "name: Mandarin Orange Anti-Bacterial Hand Sanitizer; ingredients: Ethanol; parent_key: DB00898.", + "name: Nicotac Nicotine Polacrilex Coated Cinnamon; ingredients: Nicotine; parent_key: DB00184.", + "name: TopCare Nicotine; ingredients: Nicotine; parent_key: DB00184." + ] + }, + { + "example_idx": 13, + "anchor_id": 6784909937266196771, + "positive_id": 18013629805203836028, + "join_paths": [ + [ + 14, + 46, + 0.32421875 + ], + [ + 14, + 40, + 0.318359375 + ], + [ + 14, + 8, + 0.30859375 + ], + [ + 14, + 1, + 0.2890625 + ], + [ + 14, + 48, + 0.2890625 + ] + ], + "rows": [ + "S18616 ((S)-spiro[(1-oxa-2-amino-3-azacyclopent-2-ene)-4, 2'-(8'-chloro-1',2',3',4'-tetrahydronaphthalene)]) displayed high affinity at native rat alpha(2)-adrenoceptors (AR)s (pK(i), 9.8), native human (h)alpha(2A)-ARs (9.6), and cloned halpha(2A)- (9.5), halpha(2B)- (9.2), and halpha(2C)- (9.0) ARs.", + "It showed 40-fold lower affinity for halpha(1A)-ARs (8.4) and >/=100-fold lower affinity for rat alpha(1)-ARs (7.1), halpha(1B)-ARs (7.7), halpha(1D)-ARs (7.6), imidazoline(1) (7.4), and imidazoline(2) (7.4) sites and >100-fold lower affinity for all other (>50) sites.", + "At halpha(2A)-ARs, in guanosine-5'-O-(3-[(35)S]thio)triphosphate binding studies, S18616 was a potent (partial) agonist: log effective concentration (pEC(50)), 9.3/maximal effect, 51%.", + "This observation was corroborated employing a halpha(2A)-Gi1alpha fusion protein/GTPase assay (9.0/40%) in which the actions of S18616 were blocked by pertussis toxin.", + "Employing guanosine-5'-O-(3-[(35)S]thio)triphosphate binding assays, S18616 was also a partial agonist at halpha(2C)-ARs (8.2/63%) but a full agonist (8.4/124%) at halpha(2B)-ARs.", + "At halpha(2A)-, halpha(2B)-, and halpha(2C)-ARs, the selective alpha(2)-AR antagonist, atipamezole, abolished the actions of S18616: pK(b) values of 9.1, 9.", + "1, and 9.4, respectively.", + "As determined by depletion of membrane-bound [(3)H]phosphatidyl inositols, S18616 behaved as a (less potent) agonist (7.8/79%) at halpha(1A)-ARs, an action abolished by prazosin (pK(b), 8.9).", + "Reflecting alpha(2)-AR agonist properties, S18616 potently (>/=1 microg/kg, s.c.) and dose dependently elicited hypothermia and antinociception (nine diverse models) in rodents.", + "These actions were dose dependently inhibited by chemically diverse alpha(2)- versus alpha(1)-AR antagonists, atipamezole, idazoxan, RX821,002, and BRL44418 (a preferential alpha(2A)-AR ligand).", + "In contrast, the actions of S18616 were unaffected by the alpha(1)-AR antagonists, ARC239 and prazosin (which preferentially block alpha(2B/2C)- versus alpha(2A)-ARs).", + "Although the affinity of dexmedetomidine at alpha(2)-ARs was lower than S18616; it displayed a similar receptor and functional profile.", + "Clonidine displayed lower efficacy than S18616, was substantially less potent, and had marked affinity for imidazoline(1) sites and alpha(1)-ARs.", + "In conclusion, S18616 is a novel, selective, and highly potent agonist at alpha(2)-ARs.", + "Adrenergic alpha-2 Receptor Agonists\nAdrenergic alpha-Agonists\nAnalgesics, Non-Narcotic\nAnimals\nBody Temperature\nCHO Cells\nClonidine\nCricetinae\nDexmedetomidine\nHumans\nImidazoles\nImidazoline Receptors\nMale\nMice\nOxazoles\nRats\nRats, Wistar\nReceptors, Drug" + ], + "sentences": [ + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB00692.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 10; parent_key: DB08922.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 17; parent_key: DB00246.", + "id: BE0000663; name: Retinoic acid receptor alpha; organism: Humans; known_action: unknown; position: 8; parent_key: DB00210.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 13; parent_key: DB04946.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB00484.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 19; parent_key: DB06148.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 6; parent_key: DB05271.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB00397.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 9; parent_key: DB00490.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; parent_key: DB05461.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 6; parent_key: DB06694.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 17; parent_key: DB00502.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB00935.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 10; parent_key: DB09167.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 15; parent_key: DB06153.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00925.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 15; parent_key: DB00696.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: unknown; position: 7; parent_key: DB00248.", + "id: BE0003831; name: 60S ribosomal protein L8; organism: Humans; known_action: unknown; position: 9; parent_key: DB07374.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 12; parent_key: DB00457.", + "id: BE0001519; name: Adenosylmethionine-8-amino-7-oxononanoate aminotransferase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04083.", + "id: BE0003605; name: BDNF/NT-3 growth factors receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB14723.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: yes; position: 5; parent_key: DB01363.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: no; position: 5; parent_key: DB01151.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB01018.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB01392.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; parent_key: DB05492.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: unknown; position: 5; parent_key: DB00193.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 15; parent_key: DB00408.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; parent_key: DB00800.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: yes; position: 4; parent_key: DB00852.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 16; parent_key: DB00502.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 15; parent_key: DB06216.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: no; position: 22; parent_key: DB14185.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: unknown; position: 15; parent_key: DB00502.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: no; position: 17; parent_key: DB00363.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: no; position: 6; parent_key: DB00243.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB06694.", + "id: BE0003436; name: Programmed cell death protein 1; organism: Humans; known_action: yes; position: 1; parent_key: DB09037.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB09202.", + "id: BE0001295; name: Bifunctional tail protein; organism: Enterobacteria phage P22; known_action: unknown; parent_key: DB02379.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB09242.", + "id: BE0004890; name: Muscarinic acetylcholine receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB11855.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: unknown; position: 17; parent_key: DB01403.", + "id: BE0003850; name: Reaction center protein H chain; organism: Rhodopseudomonas viridis; known_action: unknown; position: 2; parent_key: DB07392.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 5; parent_key: DB13025.", + "id: BE0000690; name: Lanosterol 14-alpha demethylase; known_action: yes; position: 13; parent_key: DB11633.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09194.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB00484." + ] + }, + { + "example_idx": 14, + "anchor_id": 955824748874500941, + "positive_id": 18225432089943498262, + "join_paths": [ + [ + 14, + 23, + 0.244140625 + ], + [ + 14, + 24, + 0.2421875 + ], + [ + 14, + 16, + 0.2412109375 + ], + [ + 14, + 40, + 0.2412109375 + ], + [ + 14, + 42, + 0.2412109375 + ] + ], + "rows": [ + "In order to satisfy government mandates, numerous studies have been performed categorizing potential endocrine disrupting chemicals as (anti)estrogens or (anti)androgens.", + "We report here that dihydrotestosterone (DHT), a potent, non-aromatizable androgen receptor agonist, induces antiestrogenic responses through direct and/or indirect modulation of vitellogenin (Vg), steroid hormone and total cytochrome P450 levels.", + "DHT and two weak, aromatizable androgens, DHEA and androstenedione (0.05-50 mg/kg per day), were fed to juvenile trout for 2 weeks.", + "DHEA and androstenedione significantly increased blood plasma Vg by up to 30- and 45-fold, respectively (P<0.05, t-test).", + "17beta-Estradiol (E2) increases were also observed with both androgens, albeit with lower sensitivity.", + "DHT markedly decreased Vg and E2 levels, suggesting that DHEA and androstenedione increased Vg and E2 via conversion to E2 and not by estrogen receptor agonism.", + "DHEA and androstenedione had no effect on total cytochrome P450 content, while DHT significantly decreased P450 content in a dose dependent fashion.", + "These results indicate that alterations in metabolism mediated by androgen receptor binding may be responsible for the Vg and E2 decreases by DHT.", + "In an attempt to decipher between receptor and non-receptor androgenic mechanisms of the observed DHT effects, DHT (0, 50 or 100 mg/kg per day) and flutamide (0-1250 mg/kg per day), an androgen receptor antagonist, were fed to juvenile rainbow trout for 2 weeks.", + "Flutamide alone was as effective as DHT in decreasing E2 and Vg levels in males but did not significantly reverse DHT induced Vg decreases in either sex (P>0.05, F-test).", + "DHT decreases in total P450 content were partially attenuated in males by flutamide co-treatment, but not females, suggesting a partial androgenic mechanism to the P450 decreases as well as a fundamental sex difference responding to androgen receptor binding.", + "Moreover, flutamide alone decreased P450 content by up to 30% in males and 40% in females.", + "These effects may be mediated through direct androgen receptor binding irrespective of whether the binding is agonistic or antagonistic.", + "This study indicates that androgen receptor agonists/antagonists can elicit significant antiestrogenic effects that may not necessarily be mediated through classic receptor binding mechanisms and signal transduction pathways.", + "Androgen Antagonists\nAndrostenedione\nAnimals\nCytochrome P-450 Enzyme System\nDehydroepiandrosterone\nDihydrotestosterone\nEstradiol\nFemale\nFlutamide\nLiver\nMale\nMicrosomes, Liver\nOncorhynchus mykiss\nReceptors, Androgen\nSex Factors\nVitellogenins" + ], + "sentences": [ + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB00499.", + "id: BE0000576; name: Penicillin-binding protein 1A; organism: Clostridium perfringens (strain 13 / Type A); known_action: yes; position: 1; parent_key: DB01147.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB04839.", + "id: BE0001111; name: Cytochrome P450 1B1; organism: Humans; known_action: unknown; position: 5; parent_key: DB06732.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB00624.", + "id: BE0000368; name: Prostaglandin E2 receptor EP2 subtype; organism: Humans; known_action: yes; position: 2; parent_key: DB09211.", + "id: BE0003760; name: Cytochrome P450; organism: Streptomyces sp. TP-A0274; known_action: unknown; position: 1; parent_key: DB07588.", + "id: BE0001111; name: Cytochrome P450 1B1; organism: Humans; known_action: unknown; position: 44; parent_key: DB14011.", + "id: BE0000277; name: Calcium-binding mitochondrial carrier protein Aralar2; organism: Humans; known_action: unknown; parent_key: DB00128.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 5; parent_key: DB00421.", + "id: BE0001111; name: Cytochrome P450 1B1; organism: Humans; known_action: unknown; position: 23; parent_key: DB04216.", + "id: BE0002707; name: Putative cytochrome P450; organism: Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145); known_action: unknown; parent_key: DB02521.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB08088.", + "id: BE0000890; name: Cyclin-dependent kinase 5; organism: Humans; known_action: unknown; parent_key: DB02950.", + "id: BE0000233; name: Cytochrome P450 51; organism: Yeast; known_action: yes; position: 2; parent_key: DB00582.", + "id: BE0002090; name: Cytochrome P450 19A1; organism: Humans; known_action: unknown; position: 15; parent_key: DB00655.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB06870.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB11619.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB11447.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB00957.", + "id: BE0004735; name: Interleukin-1 receptor antagonist protein; organism: Humans; known_action: unknown; position: 3; parent_key: DB06372.", + "id: BE0002707; name: Putative cytochrome P450; organism: Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145); known_action: unknown; parent_key: DB02175.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB01481.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB06133.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB11064.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB13934.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB01063.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB13951.", + "id: BE0003522; name: Prostaglandin E2 receptor EP4 subtype; organism: Humans; known_action: yes; position: 1; parent_key: DB12836.", + "id: BE0000675; name: Anti-Muellerian hormone type-2 receptor; organism: Humans; known_action: unknown; parent_key: DB00171.", + "id: BE0000064; name: Prostaglandin E2 receptor EP1 subtype; organism: Humans; known_action: yes; parent_key: DB00770.", + "id: BE0002433; name: Cytochrome P450 1A2; organism: Humans; known_action: unknown; position: 47; parent_key: DB14011.", + "id: BE0000311; name: 5-hydroxytryptamine receptor 3A; organism: Humans; known_action: unknown; position: 2; parent_key: DB01043.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 3; parent_key: DB04557.", + "id: BE0002090; name: Cytochrome P450 19A1; organism: Humans; known_action: yes; parent_key: DB00990.", + "id: BE0000623; name: Tyrosine-protein phosphatase non-receptor type 1; organism: Humans; known_action: unknown; parent_key: DB04088.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB13943.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; parent_key: DB05234.", + "id: BE0001111; name: Cytochrome P450 1B1; organism: Humans; known_action: unknown; position: 4; parent_key: DB07776.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB03756.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 6; parent_key: DB02266.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 5; parent_key: DB02746.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB13944.", + "id: BE0003522; name: Prostaglandin E2 receptor EP4 subtype; organism: Humans; known_action: yes; position: 3; parent_key: DB00917.", + "id: BE0001685; name: Regulatory protein E2; organism: Human papillomavirus type 11; known_action: unknown; parent_key: DB04330.", + "id: BE0000368; name: Prostaglandin E2 receptor EP2 subtype; organism: Humans; known_action: unknown; position: 1; parent_key: DB08964.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB11429.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB07419.", + "id: BE0000405; name: Muscarinic acetylcholine receptor M4; organism: Humans; known_action: no; position: 9; parent_key: DB01239.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB00858." + ] + }, + { + "example_idx": 15, + "anchor_id": 5491362822350220727, + "positive_id": 11023124076586321384, + "join_paths": [ + [ + 6, + 19, + 0.23828125 + ], + [ + 6, + 27, + 0.2373046875 + ], + [ + 6, + 41, + 0.2373046875 + ], + [ + 6, + 7, + 0.236328125 + ], + [ + 6, + 42, + 0.236328125 + ] + ], + "rows": [ + "Topotecan is a topoisomerase I inhibitor which is currently evaluated as an adjuvant agent for malignant glioma.", + "Here, we analysed the effects of topotecan on 12 human malignant glioma cell lines in vitro.", + "All cell lines expressed topoisomerase I mRNA.", + "High p53 protein levels, but not genetic or functional p53 status, were associated with increased topotecan-induced DNA/topoisomerase I complex formation.", + "Neither functional p53 status, nor p53 protein levels, nor complex formation predicted topotecan-induced growth inhibition.", + "We thus confirm a possible role for p53 protein in modulating topoisomerase I activity but conclude that the major molecular determinants of topotecan sensitivity in glioma cells await identification.", + "Antineoplastic Agents\nCell Survival\nDNA Damage\nDNA Topoisomerases, Type I\nDNA, Neoplasm\nGenes, p53\nGlioma\nHumans\nRNA, Messenger\nTopotecan\nTumor Cells, Cultured" + ], + "sentences": [ + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04858.", + "id: BE0000191; name: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB14753.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01168.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00911.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 26; parent_key: DB00321.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB04967.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB00131.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00694.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00432.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00987.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB06810.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01611.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00779.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04992.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 5; parent_key: DB00544.", + "id: BE0002459; name: Keratin, type II cytoskeletal 7; organism: Humans; known_action: unknown; parent_key: DB04959.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04996.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00305.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01103.", + "id: BE0001987; name: Divalent-cation tolerance protein CutA; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03975.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB02379.", + "id: BE0003861; name: Cytochrome b-c1 complex subunit 9; organism: Humans; known_action: unknown; position: 5; parent_key: DB07636.", + "id: BE0000217; name: Gamma-aminobutyric acid type B receptor subunit 1; organism: Humans; known_action: unknown; parent_key: DB05010.", + "id: BE0003510; name: Bcl-2-like protein 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB13044.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 2; parent_key: DB01004.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00970.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00441.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01181.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 6; parent_key: DB09327.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00236.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00488.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00614.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01123.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04950.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01265.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00888.", + "id: BE0002226; name: Voltage-dependent N-type calcium channel subunit alpha-1B; organism: Humans; known_action: yes; position: 1; parent_key: DB09232.", + "id: BE0009563; name: Transthyretin mRNA; organism: Humans; known_action: yes; position: 1; parent_key: DB14582.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01262.", + "id: BE0004701; name: NS3/4A protein; organism: Hepatitis C Virus; known_action: yes; position: 4; parent_key: DB12026.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB06421.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; position: 1; parent_key: DB00445.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB01405.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB00173.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00997.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00249.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00553.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB05245.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00385." + ] + }, + { + "example_idx": 16, + "anchor_id": 15469799003784295556, + "positive_id": 14668352177593227215, + "join_paths": [ + [ + 0, + 45, + 0.310546875 + ], + [ + 0, + 2, + 0.3046875 + ], + [ + 0, + 30, + 0.287109375 + ], + [ + 0, + 24, + 0.283203125 + ], + [ + 0, + 28, + 0.28125 + ] + ], + "rows": [ + "Paroxetine binding to the rat norepinephrine transporter in vivo.", + "Animals\nAntidepressive Agents, Second-Generation\nCarrier Proteins\nNorepinephrine\nNorepinephrine Plasma Membrane Transport Proteins\nParoxetine\nProtein Binding\nRats\nSymporters" + ], + "sentences": [ + "name: Menveo; ingredients: Neisseria meningitidis group a capsular oligosaccharide diphtheria crm197 protein conjugate antigen + Neisseria meningitidis group c capsular oligosaccharide diphtheria crm197 protein conjugate antigen + Neisseria meningitidis group w-135 capsular oligosaccharide diphtheria crm197 protein conjugate antigen + Neisseria meningitidis group y capsular oligosaccharide diphtheria crm197 protein conjugate antigen; parent_key: DB14429.", + "name: Paxil Tab 10mg; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paroxetine Hydrochloride; ingredients: Paroxetine; parent_key: DB00715.", + "name: Yellow Jacket hymenoptera venom Venomil Maintenance; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11032.", + "name: Mar-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Norepinephrine Bitartrate Injection USP; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Q-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paxil CR; ingredients: Paroxetine; parent_key: DB00715.", + "name: Dom-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paroxetine Hydrochloride Anhydrous; ingredients: Paroxetine; parent_key: DB00715.", + "name: Pharmalgen Yellow Hornet Venom; ingredients: Dolichovespula arenaria venom protein; parent_key: DB10957.", + "name: Mixed Vespid Hymenoptera Venom Multidose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB10958.", + "name: Apo-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Norepinephrine Bitartrate Injection, USP; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Sandoz Paroxetine Tablets; ingredients: Paroxetine; parent_key: DB00715.", + "name: PR Natal 430 ec; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Ferrous bisglycinate + Folic acid + Iron protein succinylate + Magnesium oxide + Nicotinamide + Omega-3 fatty acids + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB06724.", + "name: Ratio-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Yellow Jacket hymenoptera venom Venomil Maintenance; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Paroxetine-30; ingredients: Paroxetine; parent_key: DB00715.", + "name: Norepinephrine; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Mixed Vespid Hymenoptera Venom Multidose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11032.", + "name: PMS-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paxilcr CR; ingredients: Paroxetine; parent_key: DB00715.", + "name: Norepinephrine bitartrate; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Paroxetine Hydrochloride CR; ingredients: Paroxetine; parent_key: DB00715.", + "name: Prevnar 13; ingredients: Streptococcus pneumoniae type 1 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 14 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 18c capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 19a capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 19f capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 23f capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 3 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 4 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 5 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 6a capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 6b capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 7f capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 9v capsular polysaccharide diphtheria crm197 protein conjugate antigen; parent_key: DB10288.", + "name: Norepinephrine Bitartrate; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Auro-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paroxetine-10; ingredients: Paroxetine; parent_key: DB00715.", + "name: Pexeva; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paroxetine-20; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paxil; ingredients: Paroxetine; parent_key: DB00715.", + "name: Sandoz Paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paxil Tab 30mg; ingredients: Paroxetine; parent_key: DB00715.", + "name: Norepinephrine Bitartrate Inj 1mg/ml USP; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Mint-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Riva-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Levophed; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Levophed(r) Norepinephrine Bitartrate; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Levophed Liq IV 1.0mg/ml; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Act Paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Mixed Vespid hymenoptera venom Venomil Maintenance; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11030.", + "name: Teva-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Ntp-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Brisdelle; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Paxil Tab 20mg; ingredients: Paroxetine; parent_key: DB00715.", + "name: PAROXETINE HYDROCHLORIDE Controlled-Release; ingredients: Paroxetine; parent_key: DB00715.", + "name: Mylan-paroxetine; ingredients: Paroxetine; parent_key: DB00715.", + "name: Indium in 111 Oxyquinoline; ingredients: Indium In-111 oxyquinoline; parent_key: DB09473." + ] + }, + { + "example_idx": 17, + "anchor_id": 6439459923542691023, + "positive_id": 5450942951406700820, + "join_paths": [ + [ + 6, + 17, + 0.34765625 + ], + [ + 1, + 17, + 0.34375 + ], + [ + 6, + 4, + 0.32421875 + ], + [ + 6, + 23, + 0.32421875 + ], + [ + 6, + 29, + 0.31640625 + ] + ], + "rows": [ + "The low oral bioavailability of the HIV protease inhibitor (HPI) saquinavir is dramatically increased by coadministration of the HPI ritonavir.", + "Because saquinavir and ritonavir are substrates and inhibitors of both the drug transporter P-glycoprotein (P-gp) and of the metabolizing enzyme CYP3A4, we wanted to sort out whether the ritonavir effect is primarily mediated by inhibition of CYP3A4 or P-gp or both.", + "P-gp is known to limit the bioavailability, brain, testis, and fetal penetration of its substrates, so effective inhibition of P-gp by ritonavir in vivo might open up pharmacological sanctuary sites for saquinavir, with the potential of beneficial effects on therapy, but also of increased toxicity.", + "In vitro, P-gp-mediated transport of saquinavir and ritonavir was only moderately inhibited by both HPIs compared with the potent P-gp inhibitor PSC833.", + "When [(14)C]saquinavir was orally coadministered with a maximum tolerated dose of ritonavir to wild-type and P-gp-deficient mice, saquinavir bioavailability was dramatically increased in both strains, but P-gp still limited the oral bioavailability of saquinavir, and its penetration into brain and fetus.", + "These data indicate that in vivo, ritonavir is a relatively poor P-gp inhibitor.", + "The highly increased bioavailability of saquinavir because of ritonavir coadministration most likely results from reduced saquinavir metabolism.", + "Importantly, our data indicate that it is unlikely that ritonavir coadministration will substantially affect the contribution of P-gp to pharmacological sanctuary sites such as brain, testis, and fetus.", + "Thus, if one wanted to effectively open these sites for therapeutic purposes, more efficient P-gp inhibitors should be applied.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAdministration, Oral\nAnimals\nArea Under Curve\nBiological Availability\nBlood-Brain Barrier\nBrain\nCell Line\nDose-Response Relationship, Drug\nDrug Synergism\nFemale\nFetus\nHumans\nKidney\nLLC-PK1 Cells\nLiver\nMaternal-Fetal Exchange\nMice\nMice, Knockout\nPregnancy\nRitonavir\nSaquinavir\nSwine\nTransfection" + ], + "sentences": [ + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of St. John's Wort can be decreased when combined with Saquinavir.; parent_key: DB01323.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Saquinavir is combined with Bezafibrate.; parent_key: DB01393.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Busulfan can be decreased when combined with Saquinavir.; parent_key: DB01008.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of adverse effects can be increased when Saquinavir is combined with Histamine.; parent_key: DB05381.", + "drugbank-id: DB01232; name: Saquinavir; description: The serum concentration of (S)-Warfarin can be increased when it is combined with Saquinavir.; parent_key: DB14055.", + "drugbank-id: DB01232; name: Saquinavir; description: Magaldrate can cause a decrease in the absorption of Saquinavir resulting in a reduced serum concentration and potentially a decrease in efficacy.; parent_key: DB08938.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Verapamil can be decreased when combined with Saquinavir.; parent_key: DB00661.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Niacin is combined with Saquinavir.; parent_key: DB00627.", + "drugbank-id: DB00710; name: Ibandronate; description: The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Baclofen is combined with Ibandronate.; parent_key: DB00181.", + "drugbank-id: DB01232; name: Saquinavir; description: The therapeutic efficacy of Tirzepatide can be decreased when used in combination with Saquinavir.; parent_key: DB15171.", + "drugbank-id: DB08871; name: Eribulin; description: The risk or severity of bleeding can be increased when Urokinase is combined with Eribulin.; parent_key: DB00013.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Saquinavir can be decreased when combined with Prednylidene.; parent_key: DB13208.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Ciclesonide can be decreased when combined with Saquinavir.; parent_key: DB01410.", + "drugbank-id: DB00503; name: Ritonavir; description: The bioavailability of Digoxin can be increased when combined with Ritonavir.; parent_key: DB00390.", + "drugbank-id: DB01401; name: Choline magnesium trisalicylate; description: The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Choline magnesium trisalicylate is combined with Ramipril.; parent_key: DB00178.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of QTc prolongation can be increased when Tizanidine is combined with Saquinavir.; parent_key: DB00697.", + "drugbank-id: DB00503; name: Ritonavir; description: The metabolism of Ritonavir can be increased when combined with Thalidomide.; parent_key: DB01041.", + "drugbank-id: DB00503; name: Ritonavir; description: The serum concentration of Saquinavir can be increased when it is combined with Ritonavir.; parent_key: DB01232.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of QTc prolongation can be increased when Saquinavir is combined with Sultopride.; parent_key: DB13273.", + "drugbank-id: DB00631; name: Clofarabine; description: The risk or severity of bleeding can be increased when Lepirudin is combined with Clofarabine.; parent_key: DB00001.", + "drugbank-id: DB00503; name: Ritonavir; description: The metabolism of Dolutegravir can be increased when combined with Ritonavir.; parent_key: DB08930.", + "drugbank-id: DB01232; name: Saquinavir; description: The serum concentration of Saquinavir can be decreased when it is combined with Apalutamide.; parent_key: DB11901.", + "drugbank-id: DB01232; name: Saquinavir; description: The therapeutic efficacy of Lixisenatide can be decreased when used in combination with Saquinavir.; parent_key: DB09265.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Selegiline can be decreased when combined with Saquinavir.; parent_key: DB01037.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of QTc prolongation can be increased when Bupranolol is combined with Saquinavir.; parent_key: DB08808.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Alfentanil can be decreased when combined with Saquinavir.; parent_key: DB00802.", + "drugbank-id: DB01232; name: Saquinavir; description: The therapeutic efficacy of Teneligliptin can be decreased when used in combination with Saquinavir.; parent_key: DB11950.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of QTc prolongation can be increased when Coumaphos is combined with Saquinavir.; parent_key: DB11390.", + "drugbank-id: DB00503; name: Ritonavir; description: The metabolism of Thiabendazole can be increased when combined with Ritonavir.; parent_key: DB00730.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Saquinavir can be decreased when combined with Olaparib.; parent_key: DB09074.", + "drugbank-id: DB00503; name: Ritonavir; description: The metabolism of Nicotine can be decreased when combined with Ritonavir.; parent_key: DB00184.", + "drugbank-id: DB00783; name: Estradiol; description: Colestipol can cause a decrease in the absorption of Estradiol resulting in a reduced serum concentration and potentially a decrease in efficacy.; parent_key: DB00375.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Carbimazole is combined with Saquinavir.; parent_key: DB00389.", + "drugbank-id: DB09033; name: Vedolizumab; description: The risk or severity of adverse effects can be increased when Interferon alfa-2a, Recombinant is combined with Vedolizumab.; parent_key: DB00034.", + "drugbank-id: DB15349; name: Sofituzumab vedotin; description: The risk or severity of adverse effects can be increased when Adalimumab is combined with Sofituzumab vedotin.; parent_key: DB00051.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Minaprine can be decreased when combined with Saquinavir.; parent_key: DB00805.", + "drugbank-id: DB01232; name: Saquinavir; description: The therapeutic efficacy of NN344 can be decreased when used in combination with Saquinavir.; parent_key: DB05115.", + "drugbank-id: DB01232; name: Saquinavir; description: The serum concentration of Pazopanib can be increased when it is combined with Saquinavir.; parent_key: DB06589.", + "drugbank-id: DB01232; name: Saquinavir; description: Saquinavir may decrease the excretion rate of Ombitasvir which could result in a higher serum level.; parent_key: DB09296.", + "drugbank-id: DB00503; name: Ritonavir; description: The serum concentration of Avatrombopag can be increased when it is combined with Ritonavir.; parent_key: DB11995.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of QTc prolongation can be increased when Buclizine is combined with Saquinavir.; parent_key: DB00354.", + "drugbank-id: DB01232; name: Saquinavir; description: The serum concentration of Lovastatin can be increased when it is combined with Saquinavir.; parent_key: DB00227.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Nabiximols can be decreased when combined with Saquinavir.; parent_key: DB14011.", + "drugbank-id: DB01232; name: Saquinavir; description: The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Clofibrate is combined with Saquinavir.; parent_key: DB00636.", + "drugbank-id: DB09281; name: Magnesium trisilicate; description: Magnesium trisilicate can cause a decrease in the absorption of Nitrofurantoin resulting in a reduced serum concentration and potentially a decrease in efficacy.; parent_key: DB00698.", + "drugbank-id: DB10714; name: Phalaris arundinacea pollen; description: The risk of a hypersensitivity reaction to Phalaris arundinacea pollen is increased when it is combined with Carvedilol.; parent_key: DB01136.", + "drugbank-id: DB01232; name: Saquinavir; description: The serum concentration of Carbamazepine can be decreased when it is combined with Saquinavir.; parent_key: DB00564.", + "drugbank-id: DB01232; name: Saquinavir; description: The metabolism of Saquinavir can be decreased when combined with Phentermine.; parent_key: DB00191.", + "drugbank-id: DB00503; name: Ritonavir; description: The metabolism of Olaparib can be decreased when combined with Ritonavir.; parent_key: DB09074.", + "drugbank-id: DB01232; name: Saquinavir; description: The serum concentration of Saquinavir can be increased when it is combined with Morphine.; parent_key: DB00295." + ] + }, + { + "example_idx": 18, + "anchor_id": 14304854362331152806, + "positive_id": 17844876500392926761, + "join_paths": [ + [ + 0, + 20, + 0.2578125 + ], + [ + 2, + 1, + 0.25390625 + ], + [ + 0, + 5, + 0.251953125 + ], + [ + 1, + 20, + 0.251953125 + ], + [ + 11, + 25, + 0.25 + ] + ], + "rows": [ + "Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to reduce the risk and mortality of colorectal cancer (CRC).", + "Although the exact mechanisms remain unclear, the inhibition of cyclooxygenase (COX) by NSAIDs appears to abort, if not prevent, CRC carcinogenesis or metastatic tumor progression.", + "The aim of our study was to investigate the association between COX-2 expression and CRC tumor cell invasiveness.", + "The differences in immunoblot-detectable COX-2 protein contents in primary CRCs, metastatic hepatic lesions and corresponding normal mucosa from the same individual were evaluated in 17 patients.", + "Three different colon cancer cell lines, SW620, Lovo, HT-29 and a metastatic variant of HT-29, HT-29/Inv3, were employed to evaluate COX-2 expression and prostaglandin E(2) (PGE2) production in relation to their invasive abilities in vitro.", + "The effects of a COX-2-selective inhibitor, etodolac, on cell proliferation and invasive activity were also determined.", + "The results showed that 15 of 17 (88%) metastatic CRC cells from the liver and 14 of 17 (82%) primary CRC tissue exhibited much higher levels of COX-2 than corresponding adjacent normal mucosa from the same patient.", + "Among those patients with relatively high COX-2 expression in the primary tumors, almost all exhibited even higher levels of COX-2 in their hepatic metastases.", + "Among the 4 colon cancer cell lines, HT-29/Inv3 manifested the highest COX-2 expression, PGE2 production and in vitro invasive activity.", + "The selective COX-2 inhibitor, etodolac, could especially exert cytotoxicity and markedly suppress the invasive property and PGE(2) production, although not the COX-2 protein level, in HT-29/Inv3 cells.", + "Our results imply that COX-2 expression may be associated with the invasive and metastatic properties of CRC tumor cells.", + "Aged\nAged, 80 and over\nCell Division\nCell Survival\nColonic Neoplasms\nCyclooxygenase 2\nCyclooxygenase 2 Inhibitors\nCyclooxygenase Inhibitors\nDinoprostone\nEtodolac\nFemale\nHumans\nImmunoblotting\nIsoenzymes\nLiver Neoplasms\nMale\nMembrane Proteins\nMiddle Aged\nNeoplasm Invasiveness\nProstaglandin-Endoperoxide Synthases\nTumor Cells, Cultured" + ], + "sentences": [ + "ref-id: L1468; title: Anti-tumor effects of bemiparin in HepG2 and MIA PaCa-2 cells; url: https://pdfs.semanticscholar.org/e190/2ca30f2548cfa7f02e2b815705137ace90e3.pdf; parent_key: DB09258.", + "ref-id: L2966; title: Overview of selective COX-2 inhibitors; url: https://www.uptodate.com/contents/overview-of-selective-cox-2-inhibitors; parent_key: DB14059.", + "ref-id: L1161; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-propionate/testosterone-propionate-dosage/; parent_key: DB01420.", + "ref-id: L1234; title: Aspirin, Non-Aspirin Nonsteroidal Anti-inflammatory Drugs, or Acetaminophen and risk of ovarian cancer; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3454462/; parent_key: DB09212.", + "ref-id: L1881; title: Cardiovascular Effects of Tibolone: A Selective Tissue Estrogenic Activity Regulator; url: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1527-3466.2007.00007.x; parent_key: DB09070.", + "ref-id: L1227; title: Mechanism of action of non steroidal anti-inflammatory drugs; url: https://www.intechopen.com/books/nonsteroidal-anti-inflammatory-drugs/mechanism-of-action-of-nonsteroidal-anti-inflammatory-drugs; parent_key: DB09212.", + "ref-id: L8240; title: FDA Approved Drugs: Azelastine nasal spray; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020114s028lbl.pdf; parent_key: DB00972.", + "ref-id: L1478; title: A novel small-molecule inhibitor of influenza A virus acts by suppressing PA endonuclease activity of the viral polymerase; url: https://www.nature.com/articles/srep22880; parent_key: DB13997.", + "ref-id: L1492; title: Society of nuclear medicine and molecular imaging; url: http://snmmi.files.cms-plus.com/Choline%20chloride%20C-11%20(3).pdf; parent_key: DB09277.", + "ref-id: L12078; title: World Health Organization: Landscape analysis of therapeutics as of February 17 2020; url: https://www.who.int/blueprint/priority-diseases/key-action/Table_of_therapeutics_Appendix_17022020.pdf?ua=1; parent_key: DB14999.", + "ref-id: L1713; title: Pharmacokinetics of amrubicin in lung cancer patients with impaired hepatic function; url: https://www.sciencedirect.com/science/article/pii/S2213089616300603; parent_key: DB06263.", + "ref-id: L1590; title: Endocrinology association; url: https://www.thyroid.org/hyperthyroidism/; parent_key: DB09333.", + "ref-id: L2965; title: Enhancement of Tumor Response to -Radiation by an Inhibitor of Cyclooxygenase-2 Enzyme; url: https://www.researchgate.net/publication/31132809_Enhancement_of_Tumor_Response_to_-Radiation_by_an_Inhibitor_of_Cyclooxygenase-2_Enzyme; parent_key: DB14059.", + "ref-id: L2005; title: Metabolism pathway of vinorelbine (Navelbine®) in human: Characterisation of the metabolites by HPLC–MS/MS; url: https://www.sciencedirect.com/science/article/abs/pii/S0731708507007625; parent_key: DB00361.", + "ref-id: L768; title: FDA Approval Update May 17, 2017; url: https://www.drugs.com/newdrugs/fda-expands-approved-kalydeco-additional-mutations-cystic-fibrosis-4534.html?utm_source=ddc&utm_medium=email&utm_campaign=Today%27s+news+summary+-+May+18%2C+2017&utm_content=FDA+Expands+Approved+Use+of+Kalydeco+to+Treat+Additional+Mutations+of+Cystic+Fibrosis; parent_key: DB08820.", + "ref-id: L2917; title: Pharmacokinetic Study of a Single Dose of AVI-4065 in Cerebral Spinal Fluid; url: https://clinicaltrials.gov/ct2/show/NCT00381433; parent_key: DB05620.", + "ref-id: L13841; title: Deciphera phase 1 study results; url: https://www.deciphera.com/wp-content/uploads/2018/10/ESMO-2018-George-et-al.-for-submission-to-ESMO-final.pdf; parent_key: DB14840.", + "ref-id: L12153; title: NIH StatPearls: Cholesterol levels; url: https://www.ncbi.nlm.nih.gov/books/NBK542294/; parent_key: DB11936.", + "ref-id: L5789; title: Using Acetaminophen and Nonsteroidal Anti-inflammatory Drugs Safely; url: https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingOver-the-CounterMedicines/SafeUseofOver-the-CounterPainRelieversandFeverReducers/ucm164977.htm; parent_key: DB00316.", + "ref-id: L1164; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/andriol/; parent_key: DB13946.", + "ref-id: L7622; title: US Pharmacist: Cardiovascular risk associated with NSAIDS and COX2 inhibitors; url: https://www.uspharmacist.com/article/cardiovascular-risk-associated-with-nsaids-and-cox2-inhibitors; parent_key: DB00482.", + "ref-id: L1413; title: Tianeptine properties; url: http://datasheets.scbt.com/sds/aghs/en/sc-204345.pdf; parent_key: DB09289.", + "ref-id: L2107; title: Zinc homeostasis in humans; url: https://academic.oup.com/jn/article/130/5/1360S/4686372; parent_key: DB14487.", + "ref-id: L1305; title: Analgesic properties of dexketoprofen trometamol; url: https://www.researchgate.net/profile/Jean_Sebastien_Walczak/publication/260947943_Analgesic_properties_of_dexketoprofen_trometamol/links/571a523008aee3ddc568f435/Analgesic-properties-of-dexketoprofen-trometamol.pdf; parent_key: DB09214.", + "ref-id: L639; title: Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors; url: http://www.academia.edu/2570464/Trapping_of_PARP1_and_PARP2_by_Clinical_PARP_Inhibitors; parent_key: DB11793.", + "ref-id: L2962; title: Comparative Protection against Liver Inflammation and Fibrosis by a Selective Cyclooxygenase-2 Inhibitor and a Nonredox-Type 5-Lipoxygenase Inhibitor; url: http://jpet.aspetjournals.org/content/323/3/778; parent_key: DB14059.", + "ref-id: L1152; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-cypionate/; parent_key: DB13943.", + "ref-id: L1159; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-propionate/testosterone-propionate-cycle/; parent_key: DB01420.", + "ref-id: L1496; title: A gastroprotective anti-inflammatory agent: theβ-morpholinoethyl ester of niflumic acid (morniflumate); url: https://www.researchgate.net/publication/16587181_A_gastroprotective_anti-inflammatory_agent_theb-morpholinoethyl_ester_of_niflumic_acid_morniflumate; parent_key: DB09285.", + "ref-id: L1158; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-enanthate/; parent_key: DB13944.", + "ref-id: L5897; title: U.S. FDA Approves INVOKANA® (canagliflozin) to Reduce the Risk of Heart Attack, Stroke or Cardiovascular Death in Adults with Type 2 Diabetes and Established Cardiovascular Disease; url: https://www.janssen.com/us-fda-approves-invokanar-canagliflozin-reduce-risk-heart-attack-stroke-or-cardiovascular-death; parent_key: DB08907.", + "ref-id: L1009; title: Astra Zeneca Press Release: US FDA Approves Astrazeneca's Calquence for Adult Patients with Previously-Treated Mantle Cell Lymphoma; url: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2017/us-fda-approves-astrazenecas-calquence-acalabrutinib-for-adult-patients-with-previously-treated-mantle-cell-lymphoma-24102017.html#!; parent_key: DB11703.", + "ref-id: L8453; title: FDA Approved Drugs: Nintedanib; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/205832s010lbl.pdf; parent_key: DB09079.", + "ref-id: L2169; title: Influence of Lifestyle Factors on Breast Cancer Risk; url: https://www.karger.com/Article/Abstract/369571; parent_key: DB11239.", + "ref-id: L1670; title: Review of the toxicology, pharmacodynamics and pharmacokinetics of thiocolchicoside, a GABA-agonist muscle relaxant with anti-inflammatory and analgesic actions; url: https://www.researchgate.net/publication/291818675_Review_of_the_toxicology_pharmacodynamics_and_pharmacokinetics_of_thiocolchicoside_a_GABA-agonist_muscle_relaxant_with_anti-inflammatory_and_analgesic_actions; parent_key: DB11582.", + "ref-id: L13859; title: Deciphera phase 3 study results; url: https://www.deciphera.com/wp-content/uploads/2019/11/CTOS-2019-INVICTUS-Oral-Presentation-FINAL_Nov-15.pdf; parent_key: DB14840.", + "ref-id: L1580; title: Uncouplers and inhibitors; url: http://www.bmb.leeds.ac.uk/illingworth/oxphos/poisons.htm; parent_key: DB09338.", + "ref-id: L1228; title: Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036661/; parent_key: DB09212.", + "ref-id: L4672; title: Omalizumab properties, THPdb Database; url: http://crdd.osdd.net/raghava/thpdb/display_thppid_sub.php?details=Th1038; parent_key: DB00043.", + "ref-id: L1152; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-cypionate/; parent_key: DB13944.", + "ref-id: L5980; title: American Psychiatric Association; url: https://www.psychiatry.org/patients-families/depression/what-is-depression; parent_key: DB01142.", + "ref-id: L3341; title: Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression; url: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2199-z; parent_key: DB11967.", + "ref-id: L1651; title: Cancer; url: https://www.cancer.org/cancer/small-cell-lung-cancer/about/what-is-small-cell-lung-cancer.html; parent_key: DB09336.", + "ref-id: L1398; title: Monamine oxide inhibitors; url: http://www.inchem.org/documents/pims/pharm/pimg025.htm; parent_key: DB09244.", + "ref-id: L10169; title: Clinical Trial Endpoints in Cancer Research: Four Terms You Should Know; url: https://www.astrazeneca-us.com/media/astrazeneca-us-blog/2018/clinical-trial-endpoints-in-cancer-research-four-terms-you-should-know-09242018.html; parent_key: DB15035.", + "ref-id: L1152; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-cypionate/; parent_key: DB13946.", + "ref-id: L291; title: Iodophore activity, CDC; url: https://www.cdc.gov/hicpac/Disinfection_Sterilization/8_0Iodophors.html; parent_key: DB06812.", + "ref-id: L11232; title: FDA Approved Products: Sivextro (tedizolid phosphate) tablet and injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205435s000lbl.pdf; parent_key: DB09042.", + "ref-id: L3340; title: A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor; url: https://www.nature.com/articles/bjc201710; parent_key: DB11967.", + "ref-id: L11860; title: Federal Register: Withdrawal of Approval of 29 NADA's (July 3, 1996); url: https://www.govinfo.gov/content/pkg/FR-1996-07-03/html/96-16887.htm; parent_key: DB06803." + ] + }, + { + "example_idx": 19, + "anchor_id": 4703418347448070155, + "positive_id": 10590833527450669633, + "join_paths": [ + [ + 3, + 36, + 0.240234375 + ], + [ + 3, + 16, + 0.23828125 + ], + [ + 3, + 33, + 0.2373046875 + ], + [ + 3, + 10, + 0.236328125 + ], + [ + 3, + 48, + 0.236328125 + ] + ], + "rows": [ + "Fulvestrant is a 7alpha-alkylsulphinyl analogue of estradiol that competes with endogenous estrogen for binding to the estrogen receptor.", + "Once bound to the receptor, fulvestrant attenuates receptor dimerisation, effecting a rapid degradation of the estrogen receptor protein and inhibition of transcription.", + "Fulvestrant is a potent inhibitor of the growth of human breast cancer cells in vitro and in vivo.", + "It has demonstrated pure anti-estrogenic activity in animal systems.", + "Intramuscular fulvestrant 250 mg once a month was as effective as the oral aromatase inhibitor anastrozole 1 mg/day in 2 phase III trials in postmenopausal women with advanced breast cancer who had received prior endocrine therapy.", + "Median time to disease progression (the primary end-point) with fulvestrant and anastrozole was 5.4 and 3.4 months (North American trial) and 5.5 and 5.1 months (European trial).", + "The median duration of response was 19.3 and 10.5 months (North American trial) and 14.3 and 14.0 months (European trial).", + "The most common adverse events with fulvestrant are gastrointestinal disturbances and hot flushes.", + "Fulvestrant showed similar tolerability to anastrozole in 2 phase III trials.", + "Antineoplastic Agents, Hormonal\nBreast Neoplasms\nClinical Trials as Topic\nEstrogen Antagonists\nFemale\nHumans\nSteroids" + ], + "sentences": [ + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB04574.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 4; parent_key: DB00756.", + "id: BE0000575; name: Alpha-1B adrenergic receptor; organism: Humans; known_action: unknown; position: 7; parent_key: DB06144.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB07707.", + "id: BE0004367; name: CREB-binding protein; organism: Humans; known_action: unknown; position: 1; parent_key: DB08655.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB06401.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB01878.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB07087.", + "id: BE0003687; name: Penicillin-binding protein 1B; organism: Pseudomonas aeruginosa; known_action: yes; position: 1; parent_key: DB09050.", + "id: BE0003585; name: Neuronal acetylcholine receptor subunit alpha-3; organism: Humans; known_action: unknown; position: 4; parent_key: DB00472.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB13952.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB09070.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; parent_key: DB00977.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 3; parent_key: DB01108.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; position: 4; parent_key: DB01428.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB07708.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB00648.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; position: 1; parent_key: DB07757.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; parent_key: DB04573.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 3; parent_key: DB00367.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; position: 4; parent_key: DB14641.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: yes; position: 4; parent_key: DB13953.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB07932.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB08047.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00741.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB00783.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 24; parent_key: DB13944.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; parent_key: DB01645.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 14; parent_key: DB14548.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 2; parent_key: DB00304.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; position: 2; parent_key: DB00675.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB02746.", + "id: BE0004926; name: Acetylcholine receptor subunit alpha-type unc-63; organism: Caenorhabditis elegans; known_action: unknown; position: 4; parent_key: DB00848.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB02187.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB07933.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; parent_key: DB05882.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB11541.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; position: 1; parent_key: DB11674.", + "id: BE0000623; name: Tyrosine-protein phosphatase non-receptor type 1; organism: Humans; known_action: unknown; parent_key: DB03670.", + "id: BE0000247; name: Muscarinic acetylcholine receptor M5; organism: Humans; known_action: unknown; position: 21; parent_key: DB00408.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 18; parent_key: DB04216.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: yes; parent_key: DB04938.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; position: 19; parent_key: DB04216.", + "id: BE0000033; name: Insulin receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01306.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; position: 3; parent_key: DB04573.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB08048.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB06871.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB09086.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 21; parent_key: DB00624.", + "id: BE0004701; name: NS3/4A protein; organism: Hepatitis C Virus; known_action: yes; position: 1; parent_key: DB09297." + ] + }, + { + "example_idx": 20, + "anchor_id": 7661305643419708766, + "positive_id": 840670846052597241, + "join_paths": [ + [ + 2, + 10, + 0.1982421875 + ], + [ + 0, + 44, + 0.185546875 + ], + [ + 0, + 11, + 0.1845703125 + ], + [ + 0, + 48, + 0.18359375 + ], + [ + 0, + 10, + 0.1689453125 + ] + ], + "rows": [ + "The rat organic cation transporter (rOCT)-2 was characterized by electrical and tracer flux measurements compared with rOCT1.", + "By applying choline gradients to voltage-clamped Xenopus oocytes expressing rOCT2, potential-dependent currents could be induced in both directions.", + "Tracer flux measurements with seven organic cations revealed similar Michaelis-Menten constant values for both transporters, with the exception of guanidine.", + "In parallel experiments with rOCT2 and rOCT1, inhibition of tetraethylammonium transport by 12 cations, 2 weak bases, corticosterone, and the anions para-amminohippurate, alpha-ketoglutarate, and probenecid was characterized.", + "The IC(50) values of many inhibitors were similar for both transporters, whereas others were significantly different.", + "Mepiperphenidol and O-methylisoprenaline showed an approximately 70-fold lower and corticosterone a 38-fold higher affinity for rOCT2.", + "With the use of these inhibitors together with previous information on cation transporters, experimental protocols are proposed to dissect out the individual contributions of rOCT2 and rOCT1 in intact proximal tubule preparations.", + "Inhibition experiments at different pH levels strongly suggest that the weak base quinine passively permeates the plasma membrane at physiological pH and inhibits rOCT2 from the intracellular side.", + "Animals\nAnions\nCarrier Proteins\nCations\nCell Line\nCell Membrane\nCholine\nCloning, Molecular\nFemale\nGuanidine\nHistamine\nHumans\nIn Vitro Techniques\nKidney\nKinetics\nMembrane Potentials\nMembrane Proteins\nOocytes\nOrganic Cation Transport Proteins\nOrganic Cation Transporter 1\nOrganic Cation Transporter 2\nPatch-Clamp Techniques\nQuinine\nRats\nRecombinant Proteins\nTetraethylammonium\nTransfection\nXenopus laevis" + ], + "sentences": [ + "id: BE0008716; name: Voltage-dependent T-type calcium channel; organism: Humans; known_action: unknown; position: 48; parent_key: DB11093.", + "id: BE0008717; name: Voltage-dependent P/Q-type calcium channel; organism: Humans; known_action: unknown; position: 52; parent_key: DB11348.", + "id: BE0000094; name: Sodium-dependent multivitamin transporter; organism: Humans; known_action: unknown; position: 10; parent_key: DB00121.", + "id: BE0003645; name: Solute carrier family 22 member 8; organism: Humans; known_action: unknown; position: 5; parent_key: DB06710.", + "id: BE0008717; name: Voltage-dependent P/Q-type calcium channel; organism: Humans; known_action: unknown; position: 52; parent_key: DB14481.", + "id: BE0008715; name: Voltage-dependent L-type calcium channel; organism: Humans; known_action: unknown; position: 46; parent_key: DB11093.", + "id: BE0001066; name: Solute carrier family 22 member 6; organism: Humans; known_action: unknown; position: 1; parent_key: DB00812.", + "id: BE0009674; name: Solute carrier family 12 member 5; organism: Mouse; known_action: unknown; position: 4; parent_key: DB01216.", + "id: BE0002182; name: Choline transporter-like protein 4; organism: Humans; known_action: unknown; position: 14; parent_key: DB14006.", + "id: BE0000118; name: Synaptic vesicular amine transporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB01364.", + "id: BE0009848; name: Human vesicular glutamate transporters; organism: Humans; known_action: unknown; position: 6; parent_key: DB00814.", + "id: BE0008718; name: Voltage-dependent R-type calcium channel; organism: Humans; known_action: unknown; position: 54; parent_key: DB14481.", + "id: BE0000106; name: Solute carrier family 22 member 5; organism: Humans; known_action: unknown; position: 4; parent_key: DB01035.", + "id: BE0000047; name: Solute carrier family 12 member 5; organism: Humans; known_action: unknown; position: 3; parent_key: DB00761.", + "id: BE0004782; name: Solute carrier family 22 member 12; organism: Humans; known_action: unknown; position: 10; parent_key: DB00678.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: no; position: 1; parent_key: DB13092.", + "id: BE0003647; name: Solute carrier family 22 member 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB00413.", + "id: BE0008715; name: Voltage-dependent L-type calcium channel; organism: Humans; known_action: unknown; position: 51; parent_key: DB11348.", + "id: BE0003941; name: Outer membrane porin C; organism: Escherichia coli; known_action: unknown; position: 2; parent_key: DB13092.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB01017.", + "id: BE0008717; name: Voltage-dependent P/Q-type calcium channel; organism: Humans; known_action: unknown; position: 47; parent_key: DB11093.", + "id: BE0000140; name: Solute carrier family 12 member 6; organism: Humans; known_action: unknown; position: 4; parent_key: DB00761.", + "id: BE0008715; name: Voltage-dependent L-type calcium channel; organism: Humans; known_action: unknown; position: 51; parent_key: DB14481.", + "id: BE0000502; name: Solute carrier family 12 member 1; organism: Humans; known_action: no; position: 3; parent_key: DB11098.", + "id: BE0008716; name: Voltage-dependent T-type calcium channel; organism: Humans; known_action: unknown; position: 53; parent_key: DB11348.", + "id: BE0009852; name: Outer membrane porin C; organism: Escherichia coli (strain K12); known_action: unknown; position: 2; parent_key: DB01017.", + "id: BE0000276; name: Solute carrier family 12 member 7; organism: Humans; known_action: unknown; position: 5; parent_key: DB00761.", + "id: BE0000281; name: Solute carrier family 12 member 2; organism: Humans; known_action: no; position: 2; parent_key: DB11098.", + "id: BE0008716; name: Voltage-dependent T-type calcium channel; organism: Humans; known_action: unknown; position: 53; parent_key: DB14481.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 17; parent_key: DB11757.", + "id: BE0001059; name: Choline transporter-like protein 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00122.", + "id: BE0002182; name: Choline transporter-like protein 4; organism: Humans; known_action: unknown; position: 8; parent_key: DB00122.", + "id: BE0004782; name: Solute carrier family 22 member 12; organism: Humans; known_action: unknown; position: 4; parent_key: DB00870.", + "id: BE0004710; name: Solute carrier family 10 member 6; organism: Humans; known_action: unknown; position: 1; parent_key: DB02789.", + "id: BE0000601; name: Solute carrier family 12 member 4; organism: Humans; known_action: unknown; position: 6; parent_key: DB00761.", + "id: BE0001066; name: Solute carrier family 22 member 6; organism: Humans; known_action: unknown; position: 7; parent_key: DB00535.", + "id: BE0000502; name: Solute carrier family 12 member 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00761.", + "id: BE0002184; name: Choline transporter-like protein 3; organism: Humans; known_action: unknown; position: 15; parent_key: DB14006.", + "id: BE0000281; name: Solute carrier family 12 member 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB00761.", + "id: BE0004782; name: Solute carrier family 22 member 12; organism: Humans; known_action: unknown; position: 10; parent_key: DB12466.", + "id: BE0002184; name: Choline transporter-like protein 3; organism: Humans; known_action: unknown; position: 10; parent_key: DB00122.", + "id: BE0002183; name: Choline transporter-like protein 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB00122.", + "id: BE0000502; name: Solute carrier family 12 member 1; organism: Humans; known_action: yes; position: 3; parent_key: DB13620.", + "id: BE0000502; name: Solute carrier family 12 member 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB14500.", + "id: BE0008718; name: Voltage-dependent R-type calcium channel; organism: Humans; known_action: unknown; position: 54; parent_key: DB11348.", + "id: BE0001066; name: Solute carrier family 22 member 6; organism: Humans; known_action: unknown; position: 3; parent_key: DB00827.", + "id: BE0003667; name: Organic solute transporter subunit alpha; organism: Humans; known_action: unknown; position: 13; parent_key: DB00286.", + "id: BE0004782; name: Solute carrier family 22 member 12; organism: Humans; known_action: unknown; position: 23; parent_key: DB01032.", + "id: BE0008718; name: Voltage-dependent R-type calcium channel; organism: Humans; known_action: unknown; position: 49; parent_key: DB11093.", + "id: BE0001059; name: Choline transporter-like protein 1; organism: Humans; known_action: unknown; position: 13; parent_key: DB14006." + ] + }, + { + "example_idx": 21, + "anchor_id": 10182940570352398565, + "positive_id": 17481392033121608062, + "join_paths": [ + [ + 6, + 4, + 0.267578125 + ], + [ + 6, + 28, + 0.267578125 + ], + [ + 6, + 34, + 0.2578125 + ], + [ + 6, + 25, + 0.25390625 + ], + [ + 6, + 3, + 0.244140625 + ] + ], + "rows": [ + "The present study characterized the response of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP1) to chronic ritonavir (RIT) exposure by assessing increases in P-gp and MRP1 protein expression and activity.", + "LS-180V intestinal carcinoma cells were exposed for 3 days to 1-100 microM RIT concurrently with controls.", + "P-gp and MRP1 protein was quantified by Western blot analysis.", + "Cell accumulation assays, using the P-gp substrate rhodamine 123 (RH123), the P-gp/MRP1 substrate doxorubicin (DOX), and the MRP substrate carboxyfluorescein (CBF), were performed as a measure of transporter activity.", + "RIT strongly induced P-gp and MRP1 expression (maximum 6-fold and 3-fold increases, respectively) in a concentration-dependent fashion.", + "Following extended exposure to RIT (> 10 microM), cells accumulated < 50% of the RH123 and DOX compared with controls, whereas accumulation of CBF was decreased by 30% at 30 microM.", + "Differences in cell accumulation of RH123 could be eliminated with verapamil (100 microM; a P-gp inhibitor), whereas decreased DOX cell accumulation was only partially reversed by verapamil.", + "Indomethacin (100 microM; an MRP1 inhibitor) had no significant effect on RH123 or DOX accumulation, suggesting limited MRP1-mediated activity.", + "Thus, RIT induced protein expression of P-gp and MRP1 and increased cellular drug exclusion of RH123, DOX, and CBF.", + "Similar in vivo phenomena may occur during anti-HIV drug therapy, explaining potential decrements in therapeutic efficacy due to decreases in bioavailability or alterations in drug distribution.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAdenocarcinoma\nColonic Neoplasms\nDNA-Binding Proteins\nDose-Response Relationship, Drug\nHIV Protease Inhibitors\nHumans\nMembrane Transport Proteins\nMultidrug Resistance-Associated Proteins\nMutS Homolog 3 Protein\nRitonavir\nTumor Cells, Cultured" + ], + "sentences": [ + "name: Nu-verap Tab 120mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Isoptin SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Isoptin Tab 80mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil HCl; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil-120 Tab; ingredients: Verapamil; parent_key: DB00661.", + "name: Pro-verapamil SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Mylan-verapamil; ingredients: Verapamil; parent_key: DB00661.", + "name: Calan; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil Hydrochloride Injection USP; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Prevnar 13; ingredients: Corynebacterium diphtheriae + Streptococcus pneumoniae type 1 capsular polysaccharide antigen + Streptococcus pneumoniae type 14 capsular polysaccharide antigen + Streptococcus pneumoniae type 18c capsular polysaccharide antigen + Streptococcus pneumoniae type 19a capsular polysaccharide antigen + Streptococcus pneumoniae type 19f capsular polysaccharide antigen + Streptococcus pneumoniae type 23f capsular polysaccharide antigen + Streptococcus pneumoniae type 3 capsular polysaccharide antigen + Streptococcus pneumoniae type 4 capsular polysaccharide antigen + Streptococcus pneumoniae type 5 capsular polysaccharide antigen + Streptococcus pneumoniae type 6a capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 6b capsular polysaccharide antigen + Streptococcus pneumoniae type 7f capsular polysaccharide antigen + Streptococcus pneumoniae type 9v capsular polysaccharide antigen; parent_key: DB10328.", + "name: Apo-verap SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Doxorubicin Hydrochloride liposome; ingredients: Doxorubicin; parent_key: DB00997.", + "name: Taro-verapamil Tab 120mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Creon 8 Cap; ingredients: Pancrelipase amylase + Pancrelipase lipase + Pancrelipase protease; parent_key: DB11065.", + "name: Taro-doxorubicin Liposomal; ingredients: Doxorubicin; parent_key: DB00997.", + "name: Alti-verapamil - 80mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil Tab 80mg; ingredients: Verapamil; parent_key: DB00661.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB09085.", + "name: Verapamil Hydrochloride PM; ingredients: Verapamil; parent_key: DB00661.", + "name: Novo-veramil SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Covera-HS; ingredients: Verapamil; parent_key: DB00661.", + "name: Verelan; ingredients: Verapamil; parent_key: DB00661.", + "name: Isoptin Tab 120mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Verelan PM; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil Hydrochloride; ingredients: Verapamil; parent_key: DB00661.", + "name: Calan SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Nu-verap SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil; ingredients: Verapamil; parent_key: DB00661.", + "name: Nu-verap Tab 80mg; ingredients: Verapamil; parent_key: DB00661.", + "name: PMS-verapamil SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Penta-verapamil - 80mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Dom-verapamil SR 240mg Tablets; ingredients: Verapamil; parent_key: DB00661.", + "name: Apo-verap Tab 80mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil hydrochloride; ingredients: Verapamil; parent_key: DB00661.", + "name: Penta-verapamil - 120mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Apo-verap Tablet 120mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Alti-verapamil - 120mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Tuberculin Ppd (mantoux); ingredients: Tuberculin purified protein derivative; parent_key: DB11601.", + "name: Verapamil Injection 2.5mg/ml; ingredients: Verapamil; parent_key: DB00661.", + "name: Taro-verapamil Tab 80mg; ingredients: Verapamil; parent_key: DB00661.", + "name: Med Verapamil Tablets; ingredients: Verapamil; parent_key: DB00661.", + "name: Flucelvax Quadrivalent (multi-dose Vial); ingredients: Influenza A virus A/Idaho/07/2018 (H1N1) antigen (MDCK cell derived, propiolactone inactivated + Influenza A virus A/Indiana/08/2018 (H3N2) antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Iowa/06/2017 antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Singapore/INFTT-16-0610/2016 antigen (MDCK cell derived, propiolactone inactivated); parent_key: DB15506.", + "name: Remedient; ingredients: Ascorbic acid + Calcium citrate + Carnosine + Cyanocobalamin + Folic acid + Iron protein succinylate + Magnesium glycinate + Magnesium oxide + Polaprezinc + Vitamin D + Zinc; parent_key: DB09221.", + "name: Mylan-verapamil SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Venomil Inj Mixed 300mcg/dose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Riva-verapamil SR; ingredients: Verapamil; parent_key: DB00661.", + "name: Nu-indo Cap 50mg; ingredients: Indomethacin; parent_key: DB00328.", + "name: Isoptin Inj 2.5mg/ml; ingredients: Verapamil; parent_key: DB00661.", + "name: Verapamil Hci; ingredients: Verapamil; parent_key: DB00661." + ] + }, + { + "example_idx": 22, + "anchor_id": 2062400473239870717, + "positive_id": 13288224130082655572, + "join_paths": [ + [ + 13, + 43, + 0.375 + ], + [ + 1, + 43, + 0.3515625 + ], + [ + 13, + 13, + 0.349609375 + ], + [ + 0, + 43, + 0.34765625 + ], + [ + 13, + 27, + 0.34765625 + ] + ], + "rows": [ + "UNLABELLED: Quinapril is rapidly de-esterified after absorption to quinaprilat (the active diacid metabolite), a potent angiotensin converting enzyme (ACE) inhibitor.", + "Quinapril produces favourable haemodynamic changes, and improves ventricular and endothelial function in patients with various cardiovascular disorders; these effects are mediated through the binding of quinaprilat to both tissue and plasma ACE.", + "Quinapril 10 to 40 mg/day provided effective blood pressure control in most patients with essential hypertension in clinical trials, but some patients required dosages of 80 mg/day and/or concomitant diuretic therapy.", + "In general, quinapril provided similar blood pressure control to other standard antihypertensive therapies including other ACE inhibitors, calcium antagonists and beta-adrenoceptor antagonists in comparative clinical trials.", + "Combined therapy with quinapril and hydrochlorothiazide had a significantly greater antihypertensive effect than either drug as monotherapy in two well designed studies.", + "Quinapril has also been shown to reduce microalbuminuria in patients with hypertension and/or diabetes mellitus.", + "In patients with congestive heart failure, quinapril or =mepyramine>levocetirizine>cetirizine> or =terfenadine>loratadine>dextrocetirizine.", + "The inhibitory effects of cetirizine, levocetirizine, terfenadine and loratadine were slowly reversible compared to those of dextrocetirizine or mepyramine.", + "Cetirizine and its enantiomers were inactive on L-type Ca(2+) channels.", + "Reduction of the histamine H(1) receptor reserve by dibenamine in the ileum (100-fold higher than in the trachea) showed a gradual change from the competitive profile of dextrocetirizine and mepyramine to a mixed profile.", + "The present results show that cetirizine and levocetirizine are selective competitive but slowly reversible histamine H(1) receptor antagonists.", + "Their mixed antagonism profile observed in the trachea can be explained by the small receptor reserve present in this tissue compared to the ileum and their very slow dissociation rate from the histamine H(1) receptor.", + "Animals\nAorta\nCetirizine\nDose-Response Relationship, Drug\nGuinea Pigs\nHistamine\nHistamine H1 Antagonists\nIleum\nIn Vitro Techniques\nMale\nRats\nReceptors, Histamine H1\nTrachea" + ], + "sentences": [ + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 2; parent_key: DB00934.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB04837.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB00715.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB08800.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; parent_key: DB05345.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB00502.", + "id: BE0000764; name: Gamma-aminobutyric acid receptor subunit alpha-6; organism: Humans; known_action: yes; position: 5; parent_key: DB01353.", + "id: BE0003792; name: Calcium/calmodulin-dependent protein kinase type II subunit beta; organism: Humans; known_action: unknown; position: 80; parent_key: DB12010.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; parent_key: DB05492.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB04841.", + "id: BE0000451; name: 5-hydroxytryptamine receptor 2A; organism: Humans; known_action: unknown; position: 1; parent_key: DB12693.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 5; parent_key: DB00656.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00557.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 8; parent_key: DB00334.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB06282.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00967.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB01210.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 26; parent_key: DB00408.", + "id: BE0009144; name: Histamine H1 receptor; organism: Mouse; known_action: yes; position: 1; parent_key: DB11160.", + "id: BE0000059; name: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB05381.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 5; parent_key: DB01239.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 8; parent_key: DB00726.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00835.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01620.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB00246.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00920.", + "id: BE0001440; name: V-type sodium ATPase subunit K; organism: Enterococcus hirae (strain ATCC 9790 / DSM 20160 / JCM 8729 / LMG 6399 / NBRC 3181 / NCIMB 6459 / NCDO 1258); known_action: unknown; parent_key: DB02686.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01142.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; position: 5; parent_key: DB01395.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00433.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 6; parent_key: DB06016.", + "id: BE0009009; name: Calcitonin gene-related peptide type 1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB12457.", + "id: BE0003387; name: C-C chemokine receptor type 2; organism: Humans; known_action: unknown; parent_key: DB05130.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 2; parent_key: DB00458.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00748.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 10; parent_key: DB04946.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB09016.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 5; parent_key: DB00540.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01246.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB08802.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00427.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00637.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01619.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 11; parent_key: DB01238.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB08799.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB01624.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01075.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB06678.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB00964." + ] + }, + { + "example_idx": 33, + "anchor_id": 4764124049821793571, + "positive_id": 11231783583084743826, + "join_paths": [ + [ + 2, + 44, + 0.201171875 + ] + ], + "rows": [ + "\"Reaction phenotyping\" studies were performed with eletriptan (ETT) to determine its propensity to interact with coadministered medications.", + "Its ability to serve as a substrate for human P-glycoprotein (P-gp) was also investigated since a central mechanism of action has been proposed for this \"triptan\" class of drug.", + "In studies with a characterized bank of human liver microsome preparations, a good correlation (r2 = 0.932) was obtained between formation of N-desmethyl eletriptan (DETT) and CYP3A4-catalyzed testosterone 6 beta-hydroxylation.", + "DETT was selected to be monitored in our studies since it represents a significant ETT metabolite in humans, circulating at concentrations 10 to 20% of those observed for parent drug.", + "ETT was metabolized to DETT by recombinant CYP2D6 (rCYP2D6) and rCYP3A4, and to a lesser extent by rCYP2C9 and rCYP2C19.", + "The metabolism of ETT to DETT in human liver microsomes was markedly inhibited by troleandomycin, erythromycin, miconazole, and an inhibitory antibody to CYP3A4, but not by inhibitors of other major P450 enzymes.", + "ETT had little inhibitory effect on any of the P450 enzymes investigated.", + "ETT was determined to be a good substrate for human P-gp in vitro.", + "In bidirectional transport studies across LLC-MDR1 and LLC-Mdr1a cell monolayers, ETT had a BA/AB transport ratio in the range 9 to 11.", + "This finding had significance in vivo since brain exposure to ETT was reduced 40-fold in Mdr1a+/+ relative to Mdr1a-/- mice.", + "ETT metabolism to DETT is therefore catalyzed primarily by CYP3A4, and plasma concentrations are expected to be increased when coadministered with inhibitors of CYP3A4 and P-gp activity.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAnimals\nAryl Hydrocarbon Hydroxylases\nBiological Transport\nBrain\nCytochrome P-450 CYP2D6\nCytochrome P-450 CYP3A\nCytochrome P-450 Enzyme Inhibitors\nCytochrome P-450 Enzyme System\nErythromycin\nGenes, MDR\nHumans\nIndoles\nInjections, Intravenous\nMale\nMice\nMice, Mutant Strains\nMiconazole\nMicrosomes, Liver\nOxazolidinones\nOxidoreductases, N-Demethylating\nPhenotype\nPiperidines\nPyrrolidines\nRecombinant Proteins\nStatistics as Topic\nSumatriptan\nTriazoles\nTroleandomycin\nTryptamines" + ], + "sentences": [ + "name: Odan-erythromycin; ingredients: Erythromycin; parent_key: DB00199.", + "name: Beta Carotene - Tab 25000iu; ingredients: Beta carotene; parent_key: DB06755.", + "name: CareOne Miconazole 3; ingredients: Miconazole + Miconazole; parent_key: DB01110.", + "name: Vita-vim With Beta-carotene - Tab; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Choline + Copper + Cyanocobalamin + Ferrous fumarate + Folic acid + Inositol + Iodine + Magnesium + Niacin + Nicotinamide + Pantothenic acid + Pyridoxine + Racemethionine + Riboflavin + Selenium + Thiamine + Vitamin A + Vitamin E + Zinc; parent_key: DB00122.", + "name: Erythrocin Liq 250; ingredients: Erythromycin; parent_key: DB00199.", + "name: Erythrocin Filmtab 250mg; ingredients: Erythromycin; parent_key: DB00199.", + "name: Erythrocin Lactobionate; ingredients: Erythromycin; parent_key: DB00199.", + "name: Sterile Erythromycin Lactobionate Pws 500mg; ingredients: Erythromycin; parent_key: DB00199.", + "name: Novolin N; ingredients: Insulin human; parent_key: DB00030.", + "name: EryPed; ingredients: Erythromycin; parent_key: DB00199.", + "name: Pdp-erythromycin; ingredients: Erythromycin; parent_key: DB00199.", + "name: Bivigam; ingredients: Human immunoglobulin G; parent_key: DB00028.", + "name: Novo-rythro Stearate Tab 250mg; ingredients: Erythromycin; parent_key: DB00199.", + "name: Novo-rythro Ethylsuccinate Pws; ingredients: Erythromycin; parent_key: DB00199.", + "name: Erythromycine 250 Tab; ingredients: Erythromycin; parent_key: DB00199.", + "name: Erythromycin Stearate Tablets USP 250mg; ingredients: Erythromycin; parent_key: DB00199.", + "name: EryPed 400; ingredients: Erythromycin; parent_key: DB00199.", + "name: Ees 600 Tablets 600mg; ingredients: Erythromycin; parent_key: DB00199.", + "name: Androderm; ingredients: Testosterone; parent_key: DB00624.", + "name: Ilotycin; ingredients: Erythromycin; parent_key: DB00199.", + "name: Image Essentials Miconazole Treatment; ingredients: Miconazole + Miconazole; parent_key: DB01110.", + "name: Axiron; ingredients: Testosterone; parent_key: DB00624.", + "name: Ilosone Liquid 250mg/5ml; ingredients: Erythromycin; parent_key: DB00199.", + "name: Beta C & E With Selenium; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Beta carotene + Selenium; parent_key: DB11135.", + "name: Ees-200 Chewable Tbs (eryped); ingredients: Erythromycin; parent_key: DB00199.", + "name: Auro-eletriptan; ingredients: Eletriptan; parent_key: DB00216.", + "name: Erythromycin Gel; ingredients: Erythromycin; parent_key: DB00199.", + "name: Ery-Tab; ingredients: Erythromycin; parent_key: DB00199.", + "name: Maintain Multiple Vitamin & Minerals; ingredients: Beta carotene + Biotin + Calcium + Calcium ascorbate + Cholecalciferol + Choline + Chromium + Copper + Cyanocobalamin + Folic acid + Inositol + Iodine + Iron + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Potassium + Pyridoxine + Racemethionine + Riboflavin + Selenium + Thiamine + Vitamin E + Zinc; parent_key: DB00140.", + "name: Nu-erythromycin-S 250mg Tablets; ingredients: Erythromycin; parent_key: DB00199.", + "name: Novo-rythro Encap 250mg; ingredients: Erythromycin; parent_key: DB00199.", + "name: Erythro-base Tab 250mg USP; ingredients: Erythromycin; parent_key: DB00199.", + "name: Multivitamins and Minerals for Women; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Calcium Phosphate + Cholecalciferol + Choline + Chromium + Copper + Cyanocobalamin + Ferrous fumarate + Folic acid + Inositol + Magnesium + Manganese + Molybdenum + Nicotinamide + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Thiamine + Vanadium + Vitamin E + Zinc; parent_key: DB13178.", + "name: Ery-tab; ingredients: Erythromycin; parent_key: DB00199.", + "name: Ery-Ped; ingredients: Erythromycin; parent_key: DB00199.", + "name: Erythrocin Stearate; ingredients: Erythromycin; parent_key: DB00199.", + "name: Ilosone 250mg Pulvule 375; ingredients: Erythromycin; parent_key: DB00199.", + "name: Children's Chewable Tab; ingredients: alpha-Tocopherol succinate + Ascorbic acid + Beta carotene + Biotin + Chromic chloride + Cyanocobalamin + Folic acid + Magnesium + Manganese + Molybdenum + Niacin + Nicotinamide + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Racemethionine + Riboflavin + Selenious acid + Thiamine + Vitamin A + Zinc; parent_key: DB13972.", + "name: Virt-Bal DHA Plus; ingredients: Acetate + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + Doconexent + Ferrous bisglycinate + Folic acid + Icosapent + Iodine + Magnesium oxide + Nicotinamide + Pyridoxine + Riboflavin + Sodium ascorbate + Thiamine + Zinc oxide; parent_key: DB03756.", + "name: Gd-eletriptan; ingredients: Eletriptan; parent_key: DB00216.", + "name: Erythromycin Ethylsuccinate; ingredients: Erythromycin; parent_key: DB00199.", + "name: Erythromycin Base Filmtab; ingredients: Erythromycin; parent_key: DB00199.", + "name: Eryc; ingredients: Erythromycin; parent_key: DB00199.", + "name: Ilotycin Gluceptate IV Ampoule 646 1gm; ingredients: Erythromycin; parent_key: DB00199.", + "name: Testosterone Micro; ingredients: Testosterone; parent_key: DB00624.", + "name: Alti-erythromycin Tab 250mg USP; ingredients: Erythromycin; parent_key: DB00199.", + "name: Erythrocin Filmtab 500mg; ingredients: Erythromycin; parent_key: DB00199.", + "name: Men's Biomultiple Vitamin and Mineral Supplement; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Choline + Chromium + Copper + Folic acid + Inositol + Magnesium + Manganese + Methionine + Molybdenum + Nicotinamide + Pantothenic acid + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Silicon dioxide + Thiamine + Vanadium + Vitamin E + Zinc; parent_key: DB06715.", + "name: Erythro-EC; ingredients: Erythromycin; parent_key: DB00199.", + "name: PMS-erythromycin; ingredients: Erythromycin; parent_key: DB00199." + ] + }, + { + "example_idx": 34, + "anchor_id": 17926031668301165206, + "positive_id": 6695049550030899013, + "join_paths": [ + [ + 2, + 25, + 0.2197265625 + ], + [ + 2, + 10, + 0.2041015625 + ], + [ + 3, + 10, + 0.17578125 + ], + [ + 0, + 10, + 0.173828125 + ], + [ + 3, + 25, + 0.1708984375 + ] + ], + "rows": [ + "The MIC of gemifloxacin and five other quinolones was tested against 31 clinical isolates of Neisseria gonorrhoeae; strains were analyzed for the presence of mutations in both the gyrA and parC genes.", + "Only seven strains were resistant to nalidixic acid due to a mutation in the gyrA gene but not in the parC gene, with six and two considered intermediate to ciprofloxacin and levofloxacin, respectively.", + "The activity of gemifloxacin was similar to that of trovafloxacin and moxifloxacin, but was more active than nalidixic acid, ciprofloxacin or levofloxacin against the gyrA mutant strains.", + "Gemifloxacin is a valid therapeutic alternative to treat infections with N. gonorrhoeae, retaining its activity against strains already presenting a mutation in gyrA.", + "Anti-Infective Agents\nAza Compounds\nCiprofloxacin\nDNA Gyrase\nDNA Topoisomerase IV\nDrug Resistance, Bacterial\nFluoroquinolones\nGemifloxacin\nGenes, Bacterial\nGonorrhea\nHumans\nIn Vitro Techniques\nLevofloxacin\nMicrobial Sensitivity Tests\nMoxifloxacin\nMutation\nNalidixic Acid\nNaphthyridines\nNeisseria gonorrhoeae\nOfloxacin\nQuinolines" + ], + "sentences": [ + "name: Trovan Tablets 100mg; ingredients: Trovafloxacin; parent_key: DB00685.", + "name: Teva-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: Natura Magnesium Plus Vitamin C; ingredients: Ascorbic acid + Magnesium; parent_key: DB00126.", + "name: Bio-fen; ingredients: Folic acid + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin; parent_key: DB00140.", + "name: Act Ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: PMS-moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Multi-Nate 30; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + Folic acid + Iron + Magnesium oxide + Nicotinamide + Pyridoxine + Riboflavin + Thiamine + Vitamin E + Zinc oxide; parent_key: DB00140.", + "name: Bio-moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Riva-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Moxifloxacin Injection; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Jamp-moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Teva-moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Cipro Tab 100mg; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: PHL-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: PMS-levofloxacin; ingredients: Levofloxacin; parent_key: DB01137.", + "name: PMS-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: TL-Fluorivite; ingredients: Ascorbic acid + Biotin + Copper + Cyanocobalamin + Folic acid + Iron + Magnesium + Niacin + Pantothenic acid + Pyridoxine + Riboflavin + Sodium fluoride + Thiamine + Vitamin A + Vitamin D + Vitamin E + Zinc; parent_key: DB00126.", + "name: Avelox I.V.; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Dom-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Cipro; ingredients: Ciprofloxacin + Ciprofloxacin; parent_key: DB00537.", + "name: Med-moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Ciprofloxacin Tablets USP - 250 mg; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Moxifloxacin Ophthalmic Solution; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Act Moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Auro-moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Factive; ingredients: Gemifloxacin; parent_key: DB01155.", + "name: Auro-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Ciprofloxacin-250; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Mint-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Priva-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: B Compound 50mg Tab; ingredients: Biotin + Choline + Cyanocobalamin + Folic acid + Inositol + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine; parent_key: DB00121.", + "name: Bio-efa Borage Gla 90 Cap; ingredients: alpha-Linolenic acid + Gamolenic acid + Linoleic acid + Vitamin E; parent_key: DB00132.", + "name: Jamp-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Twin Ultra Liquid Lemon-lime Flavor; ingredients: Ascorbic acid + Biotin + Chromium + Nicotinamide + Pantothenic acid + Potassium + Pyridoxine + Riboflavin + Thiamine; parent_key: DB00140.", + "name: ProQuin XR; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Avelox; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Mylan-moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Mylan-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Cipro 100 - Tab 100mg; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: TL-Care DHA; ingredients: Ascorbic acid + Biotin + Cholecalciferol + Cupric sulfate + Cyanocobalamin + Doconexent + Docusate + Ferrous fumarate + Fish oil + Folic acid + Icosapent + Inositol nicotinate + Pyridoxine + Riboflavin + Thiamine + Vitamin E + Zinc sulfate; parent_key: DB00121.", + "name: Multivitamins and Minerals for Men; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Calcium Phosphate + Cholecalciferol + Choline + Chromium + Cyanocobalamin + Folic acid + Inositol + Magnesium + Manganese + Molybdenum + Nicotinamide + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Thiamine + Vanadium + Vitamin E + Zinc; parent_key: DB00115.", + "name: PHL-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Nu-ciproflox; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Ipg-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Pro-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Ciprofloxacin Otic; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Ipg-moxifloxacin; ingredients: Moxifloxacin; parent_key: DB00218.", + "name: Plenvu; ingredients: Ascorbic acid + Polyethylene glycol + Polyethylene glycol + Potassium chloride + Potassium chloride + Sodium ascorbate + Sodium chloride + Sodium chloride + Sodium sulfate; parent_key: DB00126.", + "name: Ratio-ciprofloxacin; ingredients: Ciprofloxacin; parent_key: DB00537.", + "name: Trovan; ingredients: Trovafloxacin; parent_key: DB00685." + ] + }, + { + "example_idx": 35, + "anchor_id": 5671663387830972100, + "positive_id": 8546409149205509051, + "join_paths": [ + [ + 6, + 38, + 0.302734375 + ], + [ + 6, + 1, + 0.30078125 + ], + [ + 6, + 23, + 0.30078125 + ], + [ + 6, + 30, + 0.30078125 + ], + [ + 6, + 17, + 0.298828125 + ] + ], + "rows": [ + "OBJECTIVES: Marked interpatient variability exists in blood pressure response to beta-blocker monotherapy.", + "We tested the hypothesis that 2 common polymorphisms in the gene for beta(1)-adrenergic receptor are associated with antihypertensive response to metoprolol in patients with uncomplicated hypertension.", + "METHODS: Forty hypertensive men and women aged 35 to 65 years were studied.", + "Baseline studies included 24-hour ambulatory blood pressure monitoring.", + "Patients took 50 mg metoprolol twice daily with weekly titration to response or 200 mg twice daily.", + "After a minimum of 4 weeks at stable dose, treatment phase 24-hour ambulatory blood pressure monitoring was repeated.", + "The codon 49 and 389 genotypes for beta(1)-adrenergic receptor were determined by polymerase chain reaction with restriction fragment length polymorphism.", + "Multilinear regression was performed to determine the impact of genotype and other variables on blood pressure response to metoprolol.", + "RESULTS: Patients homozygous for Arg at codon 389 had a nearly 3-fold greater reduction in daytime diastolic blood pressure (-13.3% +/- 8.4% versus -4.5% +/- 8.2%, P =.0018) compared with those who carried the variant allele.", + "The haplotype pair (diplotype) for beta(1)-adrenergic receptor was also a significant predictor of response, with patients having the Ser49Arg389/Ser49Arg389 diplotype demonstrating a decline in blood pressure of 14.7 mm Hg versus 0.5 mm Hg in patients with the Gly49Arg389/Ser49Gly389 diplotype.", + "In multiregression analysis, baseline daytime diastolic blood pressure, codon 389 genotype, and codon 49 genotype were significant predictors of blood pressure after treatment.", + "CONCLUSIONS: Our data suggest that beta(1)-adrenergic receptor polymorphisms are important determinants of antihypertensive response to metoprolol.", + "In the future, codon 49 and 389 genotypes or beta(1)-adrenergic receptor haplotypes might be used to predict the diastolic blood pressure response to metoprolol in patients with hypertension.", + "Adrenergic beta-1 Receptor Antagonists\nAdult\nAged\nAntihypertensive Agents\nFemale\nGene Frequency\nGenotype\nHumans\nHypertension\nLinear Models\nMale\nMetoprolol\nMiddle Aged\nPolymorphism, Genetic\nReceptors, Adrenergic, beta-1" + ], + "sentences": [ + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00598.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB09080.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB08807.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; position: 9; parent_key: DB00938.", + "id: BE0000013; name: Adenosine receptor A1; organism: Humans; known_action: yes; position: 3; parent_key: DB00201.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB01580.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB06148.", + "id: BE0000829; name: Glutamate receptor 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB01483.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: unknown; position: 20; parent_key: DB06216.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB06814.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB04861.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: unknown; position: 8; parent_key: DB00555.", + "id: BE0004475; name: cAMP-dependent protein kinase catalytic subunit beta; organism: Humans; known_action: unknown; parent_key: DB02482.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: unknown; position: 15; parent_key: DB00502.", + "id: BE0002341; name: Neuronal acetylcholine receptor subunit alpha-7; organism: Humans; known_action: unknown; position: 11; parent_key: DB00514.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB08558.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB08347.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: unknown; position: 19; parent_key: DB00248.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; position: 7; parent_key: DB06262.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; parent_key: DB06190.", + "id: BE0000650; name: 5-hydroxytryptamine receptor 7; organism: Humans; known_action: unknown; position: 11; parent_key: DB00246.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB00866.", + "id: BE0000478; name: Gamma-aminobutyric acid receptor subunit alpha-4; organism: Humans; known_action: yes; position: 4; parent_key: DB01354.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00335.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB04846.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB00668.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00612.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB05590.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB01288.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: unknown; position: 5; parent_key: DB00852.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB01295.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB01288.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB09204.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB01102.", + "id: BE0004797; name: GABA(A) Receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB09017.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB00960.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB00668.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00195.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00221.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB01917.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 16; parent_key: DB00543.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB01366.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00871.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: unknown; position: 7; parent_key: DB04855.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB00571.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB01102.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: unknown; position: 19; parent_key: DB06216.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB01001.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB00841.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: no; position: 1; parent_key: DB00264." + ] + }, + { + "example_idx": 36, + "anchor_id": 15361010211454750362, + "positive_id": 13227307489641206745, + "join_paths": [ + [ + 0, + 29, + 0.265625 + ], + [ + 1, + 29, + 0.25 + ], + [ + 1, + 30, + 0.22265625 + ], + [ + 0, + 30, + 0.2216796875 + ], + [ + 1, + 13, + 0.1884765625 + ] + ], + "rows": [ + "The antiestrogen, tamoxifen, has been extensively used in the treatment and prevention of breast cancer.", + "Although tamoxifen showed benefits in the chemotherapy and chemoprevention of breast cancer, epidemiological studies in both tamoxifen-treated breast cancer patients and healthy women indicated that treatment caused an increased risk of developing endometrial cancer.", + "These troubling side effects lead to concerns over long-term safety of the drug.", + "Therefore, it is important to fully understand the relationship between the antiestrogenic and the genotoxic mechanisms of tamoxifen, other antiestrogens, and their metabolites.", + "Previously, we have shown that o-quinone formation from tamoxifen and its analogues, droloxifene and 4-hydroxytoremifene, may not contribute to the cytotoxic effects of these antiestrogens; however, these o-quinones can form adducts with deoxynucleosides and this implies that the o-quinone pathway could contribute to the genotoxicity of the antiestrogens in vivo.", + "To further investigate this potential genotoxic pathway, we were interested in the role of estrogen receptor (ER)(1) alpha and beta since work with catechol estrogens has shown that ERs seem to enhance DNA damage in breast cancer cell lines.", + "As a result, we investigated the binding affinities of 4-hydroxy and 3,4-dihydroxy derivatives of tamoxifen and toremifene to ER alpha and beta.", + "The antiestrogenic activities of the metabolites using the Ishikawa cells were also investigated as well as their activity in ERalpha and ERbeta breast cancer cells using the transient transfection reporter, estrogen response element-dependent luciferase assay.", + "The data showed that the antiestrogenic activities of these compounds in the biological assays mimicked their activities in the ER binding assay.", + "To determine if the compounds were toxic and if ERs played a role in this process, the cytotoxicity of these compounds in ERbeta41(2) (ERbeta), S30 (ERalpha), and MDA-MB-231 (ER(-)) cell lines was compared.", + "The results showed that the cytotoxicity differences between the metabolites were modest.", + "In addition, all of the metabolites showed similar toxicity patterns in both ER positive and negative cell lines, which means that the ER may not contribute to the cytotoxicity pathway.", + "Finally, we compared the amount of DNA damage induced by these metabolites in these cell lines using the comet assay.", + "The catechols 3,4-dihydroxytoremifene and 3,4-dihydroxytamoxifen induced a greater amount of cellular single strand DNA cleavage as compared with the phenols in all cell lines.", + "The different amounts of DNA damage in ER positive and negative cell lines suggested that the ERs might play a role in this process.", + "These data suggest that the formation of catechols represents a minor role in cytotoxic and antiestrogenic effects in cells as compared with their phenol analogues.", + "However, catechols induced more DNA damage at nontoxic doses in breast cancer cells, which implies that o-quinones formed from catechols could contribute to genotoxicity in vivo, which is ER-dependent.", + "Binding, Competitive\nBreast Neoplasms\nCatechols\nCell Line, Tumor\nCell Survival\nComet Assay\nDNA Damage\nDrug Screening Assays, Antitumor\nEstradiol\nEstrogen Receptor Modulators\nFemale\nHumans\nIndolequinones\nQuinones\nReceptors, Estrogen\nTamoxifen\nToremifene" + ], + "sentences": [ + "ref-id: L2483; title: Advances in Skin Substitutes—Potential of Tissue Engineered Skin for Facilitating Anti-Fibrotic Healing; url: http://www.mdpi.com/2079-4983/6/3/547; parent_key: DB10771.", + "ref-id: L7913; title: FDA Label: Hydrocodone Tab ER; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206627s007s008lbl.pdf; parent_key: DB00956.", + "ref-id: L2407; title: National Cancer Institute; url: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C87662; parent_key: DB13421.", + "ref-id: L1861; title: The safety and side effects of monoclonal antibodies; url: http://theory.bio.uu.nl/immbio/pdf/TherapeuticReview2010.pdf; parent_key: DB14004.", + "ref-id: L4087; title: Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program; url: https://www.bmj.com/content/350/bmj.h454/rr-0; parent_key: DB00331.", + "ref-id: L97; title: US Biological; url: http://www.usbio.net/item/O8070-50; parent_key: DB01669.", + "ref-id: L2622; title: National Cancer Institute; url: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C61621; parent_key: DB13268.", + "ref-id: L13841; title: Deciphera phase 1 study results; url: https://www.deciphera.com/wp-content/uploads/2018/10/ESMO-2018-George-et-al.-for-submission-to-ESMO-final.pdf; parent_key: DB14840.", + "ref-id: L1929; title: Canadian cancer society; url: http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/mantle-cell-lymphoma/?region=on; parent_key: DB09053.", + "ref-id: L811; title: HSDB: Calcium Compounds; url: https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@DOCNO+6931; parent_key: DB11093.", + "ref-id: L13859; title: Deciphera phase 3 study results; url: https://www.deciphera.com/wp-content/uploads/2019/11/CTOS-2019-INVICTUS-Oral-Presentation-FINAL_Nov-15.pdf; parent_key: DB14840.", + "ref-id: L9563; title: FDA Approved Drug Products: Nasonex Mometasone Furoate Nasal Spray; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020762s053lbl.pdf; parent_key: DB14512.", + "ref-id: L10866; title: How the new Ebola vaccine was made in Canada - CBC News; url: https://www.cbc.ca/news/health/second-opinion-ebola-vaccine-1.4672807; parent_key: DB15595.", + "ref-id: L2161; title: Use of Underarm Cosmetic Products in Relation to Risk of Breast Cancer: A Case-Control Study; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514401/; parent_key: DB11239.", + "ref-id: L1651; title: Cancer; url: https://www.cancer.org/cancer/small-cell-lung-cancer/about/what-is-small-cell-lung-cancer.html; parent_key: DB09336.", + "ref-id: L14510; title: FDA News Release: FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional; url: https://www.fda.gov/news-events/press-announcements/fda-approves-breast-cancer-treatment-can-be-administered-home-health-care-professional; parent_key: DB00072.", + "ref-id: L11863; title: FDA Approved Drug Products: Sulfamethoxazole/Trimethoprim oral suspension; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/077612s005lbl.pdf; parent_key: DB00440.", + "ref-id: L2930; title: AstraZeneca: ZS-9 (sodium zirconium cyclosilicate) Phase III long-term safety and efficacy data presented at ASN Kidney Week 2017; url: https://www.astrazeneca.com/media-centre/medical-releases/zs-9-sodium-zirconium-cyclosilicate-phase-iii-long-term-safety-and-efficacy-data-presented-at-asn-kidney-week-201702112017.html; parent_key: DB14048.", + "ref-id: L2119; title: Benefits and risks of using gelatin solution as a plasma expander for perioperative and critically ill patients: A meta-analysis; url: https://www.researchgate.net/publication/221813335_Benefits_and_risks_of_using_gelatin_solution_as_a_plasma_expander_for_perioperative_and_critically_ill_patients_A_meta-analysis; parent_key: DB11242.", + "ref-id: L2168; title: BREAST CANCER AND DEODORANTS/ ANTIPERSPIRANTS: A SYSTEMATIC REVIEW; url: https://pdfs.semanticscholar.org/2877/4ce8ef9459eac3d0fb8ef8db755aa75dc492.pdf; parent_key: DB11239.", + "ref-id: L1934; title: American Cancer Society; url: https://www.cancer.org/cancer/waldenstrom-macroglobulinemia/about/what-is-wm.html; parent_key: DB09053.", + "ref-id: L2684; title: Effects of triclocarban on the transcription of estrogen, androgen and aryl hydrocarbon receptor responsive genes in human breast cancer cells; url: https://www.sciencedirect.com/science/article/pii/S0887233313000672; parent_key: DB11155.", + "ref-id: L2169; title: Influence of Lifestyle Factors on Breast Cancer Risk; url: https://www.karger.com/Article/Abstract/369571; parent_key: DB11239.", + "ref-id: L11551; title: FDA Approved Drug Products: Airduo Respiclick Fluticasone and Salmeterol Inhalation Powder; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208799s001lbl.pdf; parent_key: DB00938.", + "ref-id: L5458; title: FDA - Alpha Hydroxy Acids; url: https://www.fda.gov/cosmetics/productsingredients/ingredients/ucm107940.htm; parent_key: DB13218.", + "ref-id: L2204; title: Adverse reactions to snake antivenom, and their prevention and treatment; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767202/; parent_key: DB13905.", + "ref-id: L2271; title: Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation; url: https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bcp.12939; parent_key: DB09066.", + "ref-id: L14510; title: FDA News Release: FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional; url: https://www.fda.gov/news-events/press-announcements/fda-approves-breast-cancer-treatment-can-be-administered-home-health-care-professional; parent_key: DB14740.", + "ref-id: L2524; title: Pipradrol and derivatives; url: https://www.researchgate.net/publication/279946278_Pipradrol_and_Pipradrol_Derivatives; parent_key: DB11584.", + "ref-id: L7799; title: FDA Approved Drug Products: Tamoxifen Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/17970s37s44s49lbl.pdf; parent_key: DB00675.", + "ref-id: L7802; title: FDA Approved Drug Products: Tamoxifen Oral Solution; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021807s006lbl.pdf; parent_key: DB00675.", + "ref-id: L791; title: TOXNET Magnesium compounds; url: https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+7065; parent_key: DB09409.", + "ref-id: L2480; title: Molecular Targets of Aspirin and Cancer Prevention; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090734/; parent_key: DB11071.", + "ref-id: L1930; title: Application of Sodium Selenite in the Prevention and Treatment of Cancers; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755498/; parent_key: DB11127.", + "ref-id: L1931; title: National Cancer Institute; url: https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq; parent_key: DB09053.", + "ref-id: L2167; title: Underarm antiperspirants/deodorants and breast cancer; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797685/; parent_key: DB11239.", + "ref-id: L5933; title: Diabetes, Heart Disease, and Stroke: NIDDK; url: https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/heart-disease-stroke; parent_key: DB08907.", + "ref-id: L2165; title: Antiperspirants/Deodorants and Breast Cancer; url: https://www.cancer.gov/about-cancer/causes-prevention/risk/myths/antiperspirants-fact-sheet; parent_key: DB11239.", + "ref-id: L1557; title: National Cancer Institute; url: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/tegafur-uracil; parent_key: DB09327.", + "ref-id: L1374; title: Relationship between pharmacokinetics and pharmacodynamics of molsidomine and its metabolites in humans; url: http://europepmc.org/abstract/med/3838400; parent_key: DB09282.", + "ref-id: L2278; title: Health Canada Approved Drug Products: Sunvepra (asunaprevir) capsule; url: https://pdf.hres.ca/dpd_pm/00037935.PDF; parent_key: DB11586.", + "ref-id: L2373; title: NIH National Cancer Institute Dictionary of Cancer Terms: Anetholtrithione; url: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/anetholtrithione; parent_key: DB13853.", + "ref-id: L4588; title: Cancer.gov; url: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma; parent_key: DB11952.", + "ref-id: L12951; title: FDA News Release: FDA Approves First New Drug Under International Collaboration, A Treatment Option for Patients with HER2-Positive Metastatic Breast Cancer; url: https://www.fda.gov/news-events/press-announcements/fda-approves-first-new-drug-under-international-collaboration-treatment-option-patients-her2; parent_key: DB11652.", + "ref-id: L14510; title: FDA News Release: FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional; url: https://www.fda.gov/news-events/press-announcements/fda-approves-breast-cancer-treatment-can-be-administered-home-health-care-professional; parent_key: DB06366.", + "ref-id: L10845; title: FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies; url: https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-option-patients-her2-positive-breast-cancer-who-have-progressed-available; parent_key: DB14962.", + "ref-id: L1143; title: Tc-99m compounds; url: http://eknygos.lsmuni.lt/springer/439/173-337.pdf; parent_key: DB09139.", + "ref-id: L1678; title: Toxicokinetics of Mercury after Long-Term Repeated Exposure to Thimerosal-Containing Vaccine; url: https://watermark.silverchair.com/kfr009.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAakwggGlBgkqhkiG9w0BBwagggGWMIIBkgIBADCCAYsGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMW0bWnQIT2cgCI9grAgEQgIIBXConbxAIybSm8nt9sq3XLD6FXwk5iR6JvWmt0TZ_eNo1i23x9WAeA27ZgFUJjbtsNrf_SPnPqljOSDTHviFNpDedT1VXht8CrynwJnGIxKgYSgTlvvLMTp529pd4W1rfpurel-Dtb0SEV2z7S5DC8sgbttUwVZldRaQX-BnhUB80qyNopJumFasQtCI2fv1mVs8_jcnECqFbIHY-QMKCcsSB9VYf1hNwnF0sNqPWBVjl-bP8Za1Wjq01NGA9qQUhdZ92c5jGmyFRBhZdbxmOC-9VzwcefYnWxb3C-5DbmOgg7dy3E9o-7JKuOqJWR4Earir-bepLCUqER5TQwzJ-P3XMEWqkuZeVDC7E5mfneV-uVSk7pFVKxLYfkDxma_e-s0xwm2G0DKCPUG2gAMaOcxTaRM2ybi3dOf-X_Hks3ZhQbocEy3ngvPbkmNmnDGzHK67asKvJr9LN27wFdQ; parent_key: DB11590.", + "ref-id: L2709; title: Breast Cancer Organization, UK; url: https://www.breastcanceruk.org.uk/science-and-research/background-briefings/aluminium-salts/; parent_key: DB11200.", + "ref-id: L13712; title: FDA Approved Drug Products: Zometa Zoledronic Acid Intravenous Injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021223s041lbl.pdf; parent_key: DB00399." + ] + }, + { + "example_idx": 37, + "anchor_id": 10007881970740053073, + "positive_id": 202505325699644327, + "join_paths": [ + [ + 5, + 0, + 0.328125 + ], + [ + 4, + 0, + 0.3046875 + ], + [ + 7, + 0, + 0.2890625 + ], + [ + 3, + 0, + 0.279296875 + ], + [ + 1, + 0, + 0.271484375 + ] + ], + "rows": [ + "The chemistry, pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of alfuzosin hydrochloride in the treatment of benign prostatic hyperplasia (BPH) are discussed.", + "Alfuzosin is a functionally uroselective alpha 1-adrenergic antagonist indicated for the management of moderate to severe BPH.", + "It can improve urinary voiding symptoms and increase urinary flow rates while causing few cardiovascular adverse effects.", + "When administered as an immediate-release (IR) formulation, alfuzosin must be administered twice or thrice daily.", + "The extended-release (ER) formulations of alfuzosin for once- or twice-daily administration are associated with small variations in peak and trough serum drug levels, which may contribute to the lower frequency of cardiovascular adverse effects reported with ER versus IR alfuzosin.", + "Alfuzosin has been shown to improve patients' perception of quality of life, allowing patients to increase their physical activities and improve their ability to handle day-to-day activities.", + "Less significant improvements in patients' sense of well-being and improved sexual functioning have been reported.", + "The usual dose of alfuzosin for patients with BPH is 2.5 mg twice or thrice daily of the IR formulation or 5 mg of ER alfuzosin twice daily or 10 mg of ER alfuzosin once daily.", + "The Food and Drug Administration is currently reviewing the ER 10-mg formulation for once-daily administration.", + "IR alfuzosin is similar to all other second-generation alpha 1-adrenergic antagonists in mechanism of action, clinical efficacy, and adverse effects.", + "No dosage titration is needed for ER alfuzosin, and its onset of peak action is within days of the start of treatment.", + "Adrenergic alpha-Antagonists\nClinical Trials as Topic\nDelayed-Action Preparations\nDrug Interactions\nDrug Therapy, Combination\nFinasteride\nHumans\nMale\nProstatic Hyperplasia\nQuality of Life\nQuinazolines" + ], + "sentences": [ + "ref-id: L9251; title: FDA Approved Drug Products: Alfuzosin Extended Release Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021287s021lbl.pdf; parent_key: DB00346.", + "ref-id: L14510; title: FDA News Release: FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional; url: https://www.fda.gov/news-events/press-announcements/fda-approves-breast-cancer-treatment-can-be-administered-home-health-care-professional; parent_key: DB00072.", + "ref-id: L6193; title: PRO-TRIAZIDE (Triamterene 50 mg and Hydrochlorothiazide 25 mg) - Product Monograph; url: https://pdf.hres.ca/dpd_pm/00026038.PDF; parent_key: DB00384.", + "ref-id: L2004; title: Vinorelbine injection, Daily Med; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06eeaab8-a00d-4b41-b46b-40163f09ecb8; parent_key: DB00361.", + "ref-id: L2024; title: Chemical Summary for Hydrogen Peroxide - SSWM; url: https://www.sswm.info/sites/default/files/reference_attachments/OAK%20RIDGE%20NATIONAL%20LABORATORY%201995%20Chemical%20Summary%20of%20Hydrogen%20Peroxide.pdf; parent_key: DB11091.", + "ref-id: L1347; title: FDA Label: SilenorTM (doxepin) tablets for oral administration; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022036lbl.pdf; parent_key: DB01142.", + "ref-id: L2607; title: Mg Gluconate; url: https://www.drugs.com/ppa/magnesium-gluconate.html; parent_key: DB13749.", + "ref-id: L1524; title: Use of pipamperone and a d2-receptor antagonist or a serotonin/dopamin antagonist for the treatment of psychotic disorders; url: https://www.researchgate.net/publication/6814909_Influence_of_the_antipsychotic_drug_pipamperone_on_the_expression_of_the_dopamine_D4_receptor; parent_key: DB09286.", + "ref-id: L1828; title: Using Copper to Improve the Well-Being of the Skin; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556990/; parent_key: DB06778.", + "ref-id: L2238; title: Ferrous sulfate, Daily Med; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c0fb0c2-8c64-4dd6-adfe-74b1bf8f39c3; parent_key: DB13257.", + "ref-id: L5798; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01123486; parent_key: DB00327.", + "ref-id: L344; title: Daily med.; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6d46c03-bb1d-417b-b8e5-3bffe352fe29; parent_key: DB12332.", + "ref-id: L4894; title: FDA Approved Drug Products: Apadaz (benzhydrocodone and acetaminophen) tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208653s002s003lbl.pdf; parent_key: DB00727.", + "ref-id: L1789; title: Safety of Total Daily Doses of Polyethylene Glycol (PEG) 400 Administered Orally to Healthy Male Human Subjects; url: https://clinicaltrials.gov/ct2/show/NCT02260076; parent_key: DB11077.", + "ref-id: L4834; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02181660; parent_key: DB12141.", + "ref-id: L2302; title: Black Cohosh: Insights into its Mechanism(s) of Action; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046019/; parent_key: DB13975.", + "ref-id: L10592; title: FDA Approved Drug Products: Wellbutrin immediate-release tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018644s054lbl.pdf; parent_key: DB01156.", + "ref-id: L1796; title: Systane Mechanism of Action; url: http://www.systane.dk/professional/media/pdf/SYS_Ultra_MOA.pdf; parent_key: DB11077.", + "ref-id: L5074; title: Drug Scheduling: United States Drug Enforcement Administration (DEA); url: https://www.dea.gov/drug-scheduling; parent_key: DB00683.", + "ref-id: L11593; title: FDA Approved Drug Products: Evoclin (clindamycin phosphate) topical foam; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/050801s018lbl.pdf; parent_key: DB01190.", + "ref-id: L1168; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/record/NCT02612298?view=results; parent_key: DB09204.", + "ref-id: L1578; title: Mercurial Diuretics Their Mechanism of Action and Application; url: https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/562756?redirect=true; parent_key: DB09338.", + "ref-id: L883; title: US Drug Enforcement Administration: ETIZOLAM Drug information; url: https://www.deadiversion.usdoj.gov/drug_chem_info/etizolam.pdf; parent_key: DB09166.", + "ref-id: L4835; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02456883; parent_key: DB12141.", + "ref-id: L1497; title: Modulation of arachidonic acid metabolism by orally administered morniflumate in man; url: https://link.springer.com/article/10.1007/BF01986568; parent_key: DB09285.", + "ref-id: L2838; title: Daily Med, Pancold S; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52726d93-b3ba-432f-96f6-d03bf9f7b840; parent_key: DB11278.", + "ref-id: L493; title: Daily med; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee95aa18-9f2f-40eb-9b4c-583bea6f36bf; parent_key: DB09479.", + "ref-id: L1902; title: Summary of product characteristics; url: http://mri.cts-mrp.eu/download/DE_V_0101_001_FinalSPC.pdf; parent_key: DB11156.", + "ref-id: L5314; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT03172208; parent_key: DB06081.", + "ref-id: L2292; title: Paladin Labs - Product Monograph: SANDOMIGRAN (Pizotifen hydrogen malate 0.5 mg and 1 mg tablets); url: http://www.paladin-labs.com/our_products/Sandomigran_en.pdf; parent_key: DB06153.", + "ref-id: L5074; title: Drug Scheduling: United States Drug Enforcement Administration (DEA); url: https://www.dea.gov/drug-scheduling; parent_key: DB00395.", + "ref-id: L3626; title: FDA approves first smallpox indicated treatment; url: https://www.genengnews.com/gen-news-highlights/fda-approves-first-smallpox-indicated-treatment-sigas-tpoxx/81256026; parent_key: DB12020.", + "ref-id: L6643; title: Prochlorperazine — the forgotten antiemetic - UF Health; url: http://cdn.webservices.ufhealth.org/wp-content/blogs.dir/358/files/2011/11/0609-drugs-therapy-bulletin.pdf; parent_key: DB00433.", + "ref-id: L1376; title: Molsidomine 2/4 mg tablets; url: https://pdfs.semanticscholar.org/3cb7/a1d396f6d523af253581daf8033e64a0cb3f.pdf; parent_key: DB09282.", + "ref-id: L6370; title: EAU Stress Urinary Incontinence Guidelines; url: https://uroweb.org/guideline/urinary-incontinence/#1; parent_key: DB00476.", + "ref-id: L1898; title: Pyrantel Dosage; url: https://www.drugs.com/dosage/pyrantel.html; parent_key: DB11156.", + "ref-id: L2589; title: An evaluation of the effect ov lanolin in healing nipple injuries; url: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-21002008000100002; parent_key: DB11112.", + "ref-id: L1136; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/results/NCT02411929?sect=Xgf0156#outcome10; parent_key: DB11827.", + "ref-id: L5876; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02499146; parent_key: DB09073.", + "ref-id: L1392; title: Chemistry ; url: https://comptox.epa.gov/dashboard/dsstoxdb/results?search=Toloxatone; parent_key: DB09245.", + "ref-id: L14510; title: FDA News Release: FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional; url: https://www.fda.gov/news-events/press-announcements/fda-approves-breast-cancer-treatment-can-be-administered-home-health-care-professional; parent_key: DB14740.", + "ref-id: L2429; title: U.S. Food & Drug Administration: High-Intensity Sweeteners; url: https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm397716.htm; parent_key: DB09419.", + "ref-id: L14510; title: FDA News Release: FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional; url: https://www.fda.gov/news-events/press-announcements/fda-approves-breast-cancer-treatment-can-be-administered-home-health-care-professional; parent_key: DB06366.", + "ref-id: L11755; title: Health Canada Approved Drug Products: Desiccated Thyroid Oral Tablets; url: https://pdf.hres.ca/dpd_pm/00034857.PDF; parent_key: DB09100.", + "ref-id: L11749; title: FDA Approved Drug Products: Ajovy (fremanezumab-vfrm) subcutaneous injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761089s002lbl.pdf; parent_key: DB14041.", + "ref-id: L2604; title: Mg products; url: http://www.globalrph.com/magnesium_supplements.htm; parent_key: DB13749.", + "ref-id: L4841; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01818492; parent_key: DB14724.", + "ref-id: L2909; title: hERG potassium channel inhibition by ivabradine may contribute to QT prolongation and risk of torsades de pointes; url: http://journals.sagepub.com/doi/abs/10.1177/2042098615595546; parent_key: DB09083.", + "ref-id: L1615; title: Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina.; url: http://europepmc.org/abstract/med/26838987; parent_key: DB09363.", + "ref-id: L1738; title: U.S. Food & Drug Administration: FDA working with manufacturers to withdraw Zinbryta from the market in the United States; url: https://www.fda.gov/Drugs/DrugSafety/ucm600999.htm; parent_key: DB00111." + ] + }, + { + "example_idx": 38, + "anchor_id": 16823659044694800369, + "positive_id": 11255102675408811001, + "join_paths": [ + [ + 4, + 37, + 0.171875 + ], + [ + 4, + 24, + 0.1708984375 + ], + [ + 4, + 26, + 0.1689453125 + ], + [ + 4, + 34, + 0.166015625 + ], + [ + 4, + 31, + 0.1611328125 + ] + ], + "rows": [ + "BACKGROUND: Previous studies have shown that specific amino acid residues in the putative second transmembrane segment (TM2) of the gamma-aminobutyric acid receptor type A (GABAA) receptor play a critical role in the enhancement of GABAA receptor function by halothane, enflurane, and isoflurane.", + "However, very little is known about the actions of sevoflurane and desflurane on recombinant GABAA receptors.", + "The aim of this study was to examine the effects of sevoflurane and desflurane on potentiation of GABA-induced responses in the wild-type GABAA receptor and in receptors mutated in TM2 of the alpha1, alpha 2, or beta 2 subunits.", + "METHODS: GABAA receptor alpha 1 or alpha 2, beta 2 or beta 3, and gamma 2s subunit cDNAs were expressed for pharmacologic study by transfection of human embryonic kidney 293 cells and assayed using the whole cell voltage clamp technique.", + "Concentration-response curves and EC50 values for agonist were determined in the wild-type alpha 1 beta 2 gamma 2s and alpha 2 beta 3 gamma 2s receptors, and in receptors harboring mutations in TM2, such as alpha1(S270W)beta 2 gamma 2s, alpha 1 beta 2(N265W)gamma 2s, and alpha2(S270I)beta 3 gamma 2s.", + "The actions of clinically relevant concentration of volatile anesthetics (isoflurane, sevoflurane, and desflurane) on GABA activated Cl- currents were compared in the wild-type and mutant GABAA receptors.", + "RESULTS: Both sevoflurane and desflurane potentiated submaximal GABA currents in the wild-type GABAA alpha 1 beta 2 gamma 2s receptor and alpha 2 beta 3 gamma 2s receptor.", + "Substitution of Ser270 in TM2 of the alpha subunit by a larger amino acid, tryptophan (W) or isoleucine (I), as in alpha1(S270W)beta 2 gamma 2s and alpha 2(S270I)beta 3 gamma 2s, completely abolished the potentiation of GABA-induced currents by these anesthetic agents.", + "In contrast, mutation of Asn265 in TM2 of the beta subunit to tryptophan (W) did not prevent potentiation of GABA-induced responses.", + "The actions of sevoflurane and desflurane in the wild-type receptor and in mutated receptors were qualitatively and quantitatively similar to those observed for isoflurane.", + "CONCLUSIONS: Positions Ser270 of the GABAA alpha1 and alpha2 subunits, but not Asn265 in the TM2 of the beta2 subunit, are critical for regulation of the GABAA receptor by sevoflurane and desflurane, as well as isoflurane, consistent with the idea that these three volatile anesthetics share a common site of actions on the alpha subunit of the GABAA receptor.", + "Amino Acid Sequence\nAnesthetics, Inhalation\nCells, Cultured\nDNA, Complementary\nDesflurane\nElectrophysiology\nHumans\nIsoflurane\nMembrane Potentials\nMethyl Ethers\nMolecular Sequence Data\nMutagenesis, Site-Directed\nPatch-Clamp Techniques\nReceptors, GABA-A\nSevoflurane\nTransfection" + ], + "sentences": [ + "id: BE0002346; name: Gamma-aminobutyric acid receptor subunit beta-2; organism: Humans; known_action: yes; position: 1; parent_key: DB00818.", + "id: BE0000523; name: Gamma-aminobutyric acid receptor subunit alpha-3; organism: Humans; known_action: yes; parent_key: DB00371.", + "id: BE0000754; name: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0000285; name: Sodium-coupled neutral amino acid transporter 3; organism: Humans; known_action: unknown; parent_key: DB00117.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; parent_key: DB01353.", + "id: BE0000478; name: Gamma-aminobutyric acid receptor subunit alpha-4; organism: Humans; known_action: yes; position: 4; parent_key: DB00599.", + "id: BE0002340; name: Gamma-aminobutyric acid type B receptor subunit 2; organism: Humans; known_action: yes; position: 3; parent_key: DB08892.", + "id: BE0002345; name: Gamma-aminobutyric acid receptor subunit beta-3; organism: Humans; known_action: yes; position: 10; parent_key: DB01567.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01047.", + "id: BE0003849; name: Photosynthetic reaction center cytochrome c subunit; organism: Rhodopseudomonas viridis; known_action: unknown; position: 8; parent_key: DB04147.", + "id: BE0000764; name: Gamma-aminobutyric acid receptor subunit alpha-6; organism: Humans; known_action: yes; position: 6; parent_key: DB00312.", + "id: BE0000523; name: Gamma-aminobutyric acid receptor subunit alpha-3; organism: Humans; known_action: yes; position: 3; parent_key: DB01198.", + "id: BE0000051; name: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1; organism: Humans; known_action: unknown; position: 13; parent_key: DB14541.", + "id: BE0000217; name: Gamma-aminobutyric acid type B receptor subunit 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB02530.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; parent_key: DB01174.", + "id: BE0001290; name: Response regulator PleD; organism: Caulobacter crescentus (strain ATCC 19089 / CB15); known_action: unknown; parent_key: DB01972.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; parent_key: DB00463.", + "id: BE0000764; name: Gamma-aminobutyric acid receptor subunit alpha-6; organism: Humans; known_action: yes; position: 8; parent_key: DB00794.", + "id: BE0000738; name: Neuronal acetylcholine receptor subunit alpha-2; organism: Humans; known_action: unknown; parent_key: DB05740.", + "id: BE0000523; name: Gamma-aminobutyric acid receptor subunit alpha-3; organism: Humans; known_action: yes; position: 3; parent_key: DB01352.", + "id: BE0002345; name: Gamma-aminobutyric acid receptor subunit beta-3; organism: Humans; known_action: yes; position: 2; parent_key: DB00818.", + "id: BE0003592; name: Gamma-aminobutyric acid receptor subunit gamma-2; organism: Humans; known_action: yes; position: 6; parent_key: DB01567.", + "id: BE0000478; name: Gamma-aminobutyric acid receptor subunit alpha-4; organism: Humans; known_action: yes; position: 6; parent_key: DB01355.", + "id: BE0003250; name: Endo-1,4-beta glucanase EngF; organism: Clostridium cellulovorans; known_action: unknown; parent_key: DB02379.", + "id: BE0000381; name: Gamma-aminobutyric acid receptor subunit alpha-2; organism: Humans; known_action: yes; position: 2; parent_key: DB00599.", + "id: BE0000478; name: Gamma-aminobutyric acid receptor subunit alpha-4; organism: Humans; known_action: unknown; position: 22; parent_key: DB00898.", + "id: BE0000381; name: Gamma-aminobutyric acid receptor subunit alpha-2; organism: Humans; known_action: unknown; parent_key: DB04903.", + "id: BE0003721; name: Aryl hydrocarbon receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB08624.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; parent_key: DB00306.", + "id: BE0002345; name: Gamma-aminobutyric acid receptor subunit beta-3; organism: Humans; known_action: unknown; position: 2; parent_key: DB12458.", + "id: BE0000523; name: Gamma-aminobutyric acid receptor subunit alpha-3; organism: Humans; known_action: yes; position: 5; parent_key: DB01355.", + "id: BE0003592; name: Gamma-aminobutyric acid receptor subunit gamma-2; organism: Humans; known_action: unknown; position: 6; parent_key: DB00425.", + "id: BE0000764; name: Gamma-aminobutyric acid receptor subunit alpha-6; organism: Humans; known_action: yes; position: 8; parent_key: DB01355.", + "id: BE0000764; name: Gamma-aminobutyric acid receptor subunit alpha-6; organism: Humans; known_action: yes; position: 6; parent_key: DB01354.", + "id: BE0000381; name: Gamma-aminobutyric acid receptor subunit alpha-2; organism: Humans; known_action: yes; position: 3; parent_key: DB00849.", + "id: BE0000523; name: Gamma-aminobutyric acid receptor subunit alpha-3; organism: Humans; known_action: unknown; position: 2; parent_key: DB00425.", + "id: BE0000471; name: Gamma-aminobutyric acid receptor subunit alpha-5; organism: Humans; known_action: yes; position: 4; parent_key: DB01353.", + "id: BE0000381; name: Gamma-aminobutyric acid receptor subunit alpha-2; organism: Humans; known_action: yes; position: 2; parent_key: DB01354.", + "id: BE0002346; name: Gamma-aminobutyric acid receptor subunit beta-2; organism: Humans; known_action: yes; position: 9; parent_key: DB01567.", + "id: BE0000764; name: Gamma-aminobutyric acid receptor subunit alpha-6; organism: Humans; known_action: yes; position: 5; parent_key: DB00306.", + "id: BE0000217; name: Gamma-aminobutyric acid type B receptor subunit 1; organism: Humans; known_action: yes; position: 2; parent_key: DB08892.", + "id: BE0000523; name: Gamma-aminobutyric acid receptor subunit alpha-3; organism: Humans; known_action: unknown; parent_key: DB05087.", + "id: BE0002345; name: Gamma-aminobutyric acid receptor subunit beta-3; organism: Humans; known_action: unknown; position: 42; parent_key: DB00898.", + "id: BE0000557; name: Progesterone receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00294.", + "id: BE0000217; name: Gamma-aminobutyric acid type B receptor subunit 1; organism: Humans; known_action: yes; position: 1; parent_key: DB08891.", + "id: BE0000764; name: Gamma-aminobutyric acid receptor subunit alpha-6; organism: Humans; known_action: yes; position: 5; parent_key: DB00463.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; position: 1; parent_key: DB01496.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; position: 1; parent_key: DB01354.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; position: 1; parent_key: DB00312.", + "id: BE0000217; name: Gamma-aminobutyric acid type B receptor subunit 1; organism: Humans; known_action: yes; parent_key: DB00837." + ] + }, + { + "example_idx": 39, + "anchor_id": 12064952500163843918, + "positive_id": 15816726519324033490, + "join_paths": [ + [ + 0, + 47, + 0.328125 + ], + [ + 0, + 32, + 0.326171875 + ], + [ + 5, + 32, + 0.255859375 + ], + [ + 5, + 47, + 0.25390625 + ], + [ + 5, + 38, + 0.2294921875 + ] + ], + "rows": [ + "In cerebral cortex and lateral septal nuclei different serotonergic receptor subtypes coexist, thus a different action on neuronal firing may be expected depending on the receptor activated.", + "Dorsal raphe nucleus stimulation produced an increased rate of firing in cortical layer V, and in lateral septal nuclei.", + "However, firing rate in cortical layer VI remained unchanged after stimulating the dorsal raphe nucleus.", + "Clomipramine is a tricyclic which exerts its main actions on serotonergic receptors, and long-term treatment with this antidepressant produced a selective increased firing rate in lateral septal neurons, but not in cortical neurons.", + "From an electrophysiological point of view, it is concluded that the excitatory actions on firing rate elicited by dorsal raphe nucleus stimulation or clomipramine treatment are mediated by 5-HT2 receptor subtype activation which is likely to be acting as a 5-HT1A modulator in such places where both receptor subtypes coexist.", + "Action Potentials\nAnimals\nCerebral Cortex\nClomipramine\nElectric Stimulation\nMale\nRaphe Nuclei\nRats\nRats, Wistar\nReceptors, Serotonin\nSeptal Nuclei" + ], + "sentences": [ + "id: BE0000628; name: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha; organism: Humans; known_action: unknown; parent_key: DB05194.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB00397.", + "id: BE0000767; name: Epidermal growth factor receptor; organism: Humans; known_action: yes; position: 9; parent_key: DB11963.", + "id: BE0000628; name: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha; organism: Humans; known_action: yes; position: 3; parent_key: DB10772.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB06707.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 9; parent_key: DB00715.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 16; parent_key: DB06153.", + "id: BE0000853; name: Macrophage colony-stimulating factor 1 receptor; organism: Humans; known_action: unknown; position: 5; parent_key: DB00619.", + "id: BE0000327; name: Melatonin receptor type 1B; organism: Humans; known_action: yes; position: 3; parent_key: DB06594.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB11477.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 14; parent_key: DB00477.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 8; parent_key: DB01175.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 12; parent_key: DB00457.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB13025.", + "id: BE0000369; name: Vascular endothelial growth factor receptor 2; organism: Humans; known_action: unknown; parent_key: DB05984.", + "id: BE0000793; name: Granulocyte colony-stimulating factor receptor; organism: Humans; known_action: unknown; parent_key: DB05249.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 23; parent_key: DB00543.", + "id: BE0000628; name: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha; organism: Humans; known_action: unknown; position: 4; parent_key: DB11338.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 2; parent_key: DB00841.", + "id: BE0002481; name: Granulocyte-macrophage colony-stimulating factor; organism: Humans; known_action: unknown; parent_key: DB05194.", + "id: BE0000650; name: 5-hydroxytryptamine receptor 7; organism: Humans; known_action: unknown; position: 11; parent_key: DB00363.", + "id: BE0000043; name: Endothelin B receptor; organism: Humans; known_action: unknown; parent_key: DB06138.", + "id: BE0000853; name: Macrophage colony-stimulating factor 1 receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB07202.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 5; parent_key: DB13025.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 6; parent_key: DB01175.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB00433.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB09204.", + "id: BE0000387; name: Follicle-stimulating hormone receptor; organism: Humans; known_action: yes; parent_key: DB00094.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: no; position: 7; parent_key: DB00934.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 16; parent_key: DB00193.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 19; parent_key: DB06148.", + "id: BE0009004; name: Nodal modulator 1; organism: Humans; known_action: unknown; position: 14; parent_key: DB00277.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB01049.", + "id: BE0000853; name: Macrophage colony-stimulating factor 1 receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB12978.", + "id: BE0000365; name: Glutamate receptor ionotropic, NMDA 1; organism: Humans; known_action: unknown; position: 9; parent_key: DB06151.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 9; parent_key: DB00490.", + "id: BE0000915; name: Hepatocyte growth factor receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB06997.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 6; parent_key: DB05271.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB06678.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 28; parent_key: DB01136.", + "id: BE0000628; name: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha; organism: Humans; known_action: unknown; position: 8; parent_key: DB10770.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09194.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 19; parent_key: DB01151.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09203.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00496.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 3; parent_key: DB09286.", + "id: BE0000387; name: Follicle-stimulating hormone receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00097.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB11273.", + "id: BE0000793; name: Granulocyte colony-stimulating factor receptor; organism: Humans; known_action: yes; parent_key: DB00099.", + "id: BE0000793; name: Granulocyte colony-stimulating factor receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB13200." + ] + }, + { + "example_idx": 40, + "anchor_id": 6457960416576710846, + "positive_id": 16579100421930501973, + "join_paths": [ + [ + 15, + 10, + 0.36328125 + ], + [ + 15, + 29, + 0.359375 + ], + [ + 3, + 21, + 0.353515625 + ], + [ + 6, + 26, + 0.353515625 + ], + [ + 15, + 26, + 0.3515625 + ] + ], + "rows": [ + "The clinical pharmacokinetics and pharmacokinetic/dynamic properties of the beta-adrenergic drugs fenoterol, salbutamol and terbutaline are reviewed.", + "Sulfate conjugates are the main metabolites in man.", + "The protein binding of these derivatives is rather weak with most pronounced binding observed e.g.", + "fenoterol (40%).", + "Disposition after parenteral administration shows a multi-exponential behavior for all the substances with linear but also stereo-selective pharmacokinetics.", + "After parenteral administration, the drugs are mainly eliminated by renal processes while after oral administration a pronounced metabolic clearance (high first pass effect) is responsible for a low bioavailability, especially for fenoterol (2%).", + "The total clearance for fenoterol is about twice that of salbutamol and terbutaline.", + "Seven to 15% of the delivered aerosol reach typically the systemic circulation.", + "In patients with respiratory disorders, pulmonary absorption is however highly dependent on the disease state.", + "Pharmacokinetics in children do not significantly differ from adults when expressed per kg body weight.", + "Patients with renal failure but not asthmatics show changed pharmacokinetic profiles.", + "Only insignificant interactions with other drugs have been found.", + "Pharmacokinetic/dynamic modeling approaches indicated that fenoterol is 25 times more active at the site of action than salbutamol and terbutaline, but all three drugs show similar bronchopulmonary selectivities.", + "When the overall clinical activity, determined by pharmacokinetic and dynamic properties is compared, the activity gap is reduced: fenoterol (8) greater than salbutamol (2) greater than terbutaline (1).", + "Differences in the first pass effect even inverse the pattern after oral administration.", + "PK/PD modeling quantified the pulmonary effect after inhalation and suggested that the higher incidence of side effects for fenoterol might be linked to an overdosing problem.", + "The application of PK/PD principles may improve the clinical usage and therapy of beta-2-adrenergic drugs.", + "Adrenergic beta-Agonists\nAdult\nAlbuterol\nChild\nFenoterol\nHumans\nTerbutaline" + ], + "sentences": [ + "drugbank-id: DB01288; name: Fenoterol; description: The therapeutic efficacy of Fenoterol can be decreased when used in combination with Asenapine.; parent_key: DB06216.", + "drugbank-id: DB01328; name: Cefonicid; description: The therapeutic efficacy of Urokinase can be decreased when used in combination with Cefonicid.; parent_key: DB00013.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Midodrine is combined with Fenoterol.; parent_key: DB00211.", + "drugbank-id: DB01288; name: Fenoterol; description: Fenoterol may decrease the antihypertensive activities of Tadalafil.; parent_key: DB00820.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypertension can be increased when Fenoterol is combined with Lurasidone.; parent_key: DB08815.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Bambuterol is combined with Fenoterol.; parent_key: DB01408.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Prifinium.; parent_key: DB13254.", + "drugbank-id: DB00501; name: Cimetidine; description: Tositumomab may decrease the excretion rate of Cimetidine which could result in a higher serum level.; parent_key: DB00081.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypertension can be increased when Tolmetin is combined with Fenoterol.; parent_key: DB00500.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Phenglutarimide.; parent_key: DB13413.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypokalemia can be increased when Halometasone is combined with Fenoterol.; parent_key: DB13728.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Batefenterol.; parent_key: DB12526.", + "drugbank-id: DB01288; name: Fenoterol; description: The therapeutic efficacy of Methylcellulose can be decreased when used in combination with Fenoterol.; parent_key: DB11228.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Valomaciclovir.; parent_key: DB06575.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypokalemia can be increased when Fluperolone is combined with Fenoterol.; parent_key: DB13491.", + "drugbank-id: DB00586; name: Diclofenac; description: The risk or severity of bleeding and hemorrhage can be increased when Diclofenac is combined with Urokinase.; parent_key: DB00013.", + "drugbank-id: DB11312; name: Protein C; description: The risk or severity of bleeding and bruising can be increased when Protein C is combined with Ursodeoxycholic acid.; parent_key: DB01586.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Pargyline is combined with Fenoterol.; parent_key: DB01626.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Methimazole.; parent_key: DB00763.", + "drugbank-id: DB05143; name: OXI-4503; description: Sucralfate can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy.; parent_key: DB00364.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Oxyphenonium is combined with Fenoterol.; parent_key: DB00219.", + "drugbank-id: DB01288; name: Fenoterol; description: Fenoterol may decrease the antihypertensive activities of Eplerenone.; parent_key: DB00700.", + "drugbank-id: DB01288; name: Fenoterol; description: The therapeutic efficacy of Fenoterol can be decreased when used in combination with Levobetaxolol.; parent_key: DB09351.", + "drugbank-id: DB01288; name: Fenoterol; description: Fenoterol may decrease the antihypertensive activities of Guanoclor.; parent_key: DB13779.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Barbital.; parent_key: DB01483.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Levorphanol.; parent_key: DB00854.", + "drugbank-id: DB01288; name: Fenoterol; description: The therapeutic efficacy of Fenoterol can be decreased when used in combination with Procaine.; parent_key: DB00721.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypertension can be increased when Carprofen is combined with Fenoterol.; parent_key: DB00821.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Etilefrine.; parent_key: DB08985.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypokalemia can be increased when Cloprednol is combined with Fenoterol.; parent_key: DB13843.", + "drugbank-id: DB01288; name: Fenoterol; description: The therapeutic efficacy of Lubiprostone can be decreased when used in combination with Fenoterol.; parent_key: DB01046.", + "drugbank-id: DB00184; name: Nicotine; description: The risk or severity of adverse effects can be increased when Botulinum Toxin Type B is combined with Nicotine.; parent_key: DB00042.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Escitalopram is combined with Fenoterol.; parent_key: DB01175.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Alfentanil.; parent_key: DB00802.", + "drugbank-id: DB01288; name: Fenoterol; description: The therapeutic efficacy of Fenoterol can be decreased when used in combination with Ziprasidone.; parent_key: DB00246.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Dopamine is combined with Fenoterol.; parent_key: DB00988.", + "drugbank-id: DB00559; name: Bosentan; description: The serum concentration of Amprenavir, an active metabolite of Fosamprenavir, can be decreased when used in combination with Bosentan.; parent_key: DB01319.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypokalemia can be increased when Deflazacort is combined with Fenoterol.; parent_key: DB11921.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypertension can be increased when Imipramine is combined with Fenoterol.; parent_key: DB00458.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypertension can be increased when Ibuprofen is combined with Fenoterol.; parent_key: DB01050.", + "drugbank-id: DB13481; name: Tenidap; description: The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Tenidap is combined with Quinapril.; parent_key: DB00881.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with 7-Deazaguanine.; parent_key: DB02245.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypertension can be increased when Fenoterol is combined with Cimicoxib.; parent_key: DB05095.", + "drugbank-id: DB01288; name: Fenoterol; description: The therapeutic efficacy of Fenoterol can be decreased when used in combination with Betahistine.; parent_key: DB06698.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypertension can be increased when Fenoterol is combined with Aminophenazone.; parent_key: DB01424.", + "drugbank-id: DB01288; name: Fenoterol; description: The therapeutic efficacy of Fenoterol can be decreased when used in combination with Thiotepa.; parent_key: DB04572.", + "drugbank-id: DB00531; name: Cyclophosphamide; description: The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Cyclophosphamide.; parent_key: DB00068.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Benzilone.; parent_key: DB13369.", + "drugbank-id: DB01288; name: Fenoterol; description: The risk or severity of hypokalemia can be increased when Fenoterol is combined with Azosemide.; parent_key: DB08961.", + "drugbank-id: DB00057; name: Indium In-111 satumomab pendetide; description: The risk or severity of adverse effects can be increased when Adalimumab is combined with Indium In-111 satumomab pendetide.; parent_key: DB00051." + ] + }, + { + "example_idx": 42, + "anchor_id": 6273742685132119571, + "positive_id": 767617727225772812, + "join_paths": [ + [ + 5, + 48, + 0.1689453125 + ] + ], + "rows": [ + "Imiquimod is a topical immune response modifier that binds to Toll-like receptor-7 and -8, inducing interferon-alpha.", + "We treated superficial basal cell carcinomas (BCC) with imiquimod 5% cream daily for 5-8 days.", + "The BCC lesions were biopsied before treatment and following imiquimod treatment, when the lesion showed the signs of erosion.", + "We applied histology, immunohistochemistry and gene array technology (Affymetrix) to gain further insight into the mode of action of imiquimod.", + "Our findings demonstrate that imiquimod-induced BCC regression is associated with a strong activity of the innate immune response, mediated by cells of macrophage-monocyte origin and is associated with the induction of apoptosis.", + "Adjuvants, Immunologic\nAminoquinolines\nApoptosis\nCarcinoma, Basal Cell\nCytokines\nDendritic Cells\nGene Expression\nHumans\nImiquimod\nImmunotherapy, Active\nSkin Neoplasms" + ], + "sentences": [ + "id: BE0009445; name: Cyclin-G-associated kinase; organism: Humans; known_action: unknown; position: 145; parent_key: DB12010.", + "id: BE0000155; name: Toll-like receptor 7; organism: Humans; known_action: unknown; parent_key: DB06530.", + "id: BE0000575; name: Alpha-1B adrenergic receptor; organism: Humans; known_action: unknown; position: 9; parent_key: DB00590.", + "id: BE0003788; name: Death-associated protein kinase 3; organism: Humans; known_action: unknown; position: 1; parent_key: DB07125.", + "id: BE0004634; name: Interferon-inducible GTPase 5; organism: Humans; known_action: unknown; parent_key: DB03814.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB07717.", + "id: BE0001171; name: Toll-like receptor 9; organism: Humans; known_action: unknown; parent_key: DB05475.", + "id: BE0002123; name: Retinoblastoma-associated protein; organism: Humans; known_action: unknown; position: 6; parent_key: DB00071.", + "id: BE0001290; name: Response regulator PleD; organism: Caulobacter crescentus (strain ATCC 19089 / CB15); known_action: unknown; parent_key: DB01972.", + "id: BE0002123; name: Retinoblastoma-associated protein; organism: Humans; known_action: unknown; position: 4; parent_key: DB00030.", + "id: BE0000661; name: Interferon alpha/beta receptor 1; organism: Humans; known_action: yes; parent_key: DB00034.", + "id: BE0000661; name: Interferon alpha/beta receptor 1; organism: Humans; known_action: yes; parent_key: DB00018.", + "id: BE0003788; name: Death-associated protein kinase 3; organism: Humans; known_action: unknown; position: 1; parent_key: DB04716.", + "id: BE0002136; name: Vesicle-associated membrane protein 1; organism: Humans; known_action: yes; position: 2; parent_key: DB00042.", + "id: BE0002442; name: Toll-like receptor 4; organism: Humans; known_action: yes; position: 1; parent_key: DB13615.", + "id: BE0001171; name: Toll-like receptor 9; organism: Humans; known_action: unknown; parent_key: DB05530.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; parent_key: DB00959.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB06718.", + "id: BE0000155; name: Toll-like receptor 7; organism: Humans; known_action: yes; parent_key: DB00724.", + "id: BE0009409; name: AP2-associated protein kinase 1; organism: Humans; known_action: unknown; position: 58; parent_key: DB12010.", + "id: BE0001016; name: Rho-associated protein kinase 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB08162.", + "id: BE0003475; name: Microtubule-associated protein 4; organism: Humans; known_action: yes; position: 6; parent_key: DB01248.", + "id: BE0003767; name: S-phase kinase-associated protein 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB06982.", + "id: BE0000476; name: 5-hydroxytryptamine receptor 1E; organism: Humans; known_action: unknown; position: 6; parent_key: DB01224.", + "id: BE0000861; name: Receptor activity-modifying protein 3; organism: Humans; known_action: yes; position: 4; parent_key: DB01278.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB07996.", + "id: BE0009452; name: Interleukin-1 receptor-associated kinase 1; organism: Humans; known_action: unknown; position: 156; parent_key: DB12010.", + "id: BE0003518; name: Toll-like receptor 8; organism: Humans; known_action: unknown; position: 1; parent_key: DB00724.", + "id: BE0000965; name: Apoptosis-inducing factor 1, mitochondrial; organism: Humans; known_action: unknown; parent_key: DB03147.", + "id: BE0000944; name: Interferon gamma; organism: Humans; known_action: yes; position: 6; parent_key: DB10772.", + "id: BE0009453; name: Interleukin-1 receptor-associated kinase 3; organism: Humans; known_action: unknown; position: 157; parent_key: DB12010.", + "id: BE0004573; name: Ubiquitin-like modifier-activating enzyme 1; organism: Humans; known_action: unknown; position: 32; parent_key: DB04216.", + "id: BE0001100; name: Microtubule-associated protein 2; organism: Humans; known_action: yes; parent_key: DB01196.", + "id: BE0000385; name: Interferon alpha/beta receptor 2; organism: Humans; known_action: yes; position: 3; parent_key: DB06152.", + "id: BE0001776; name: Death-associated protein kinase 1; organism: Humans; known_action: unknown; position: 104; parent_key: DB12010.", + "id: BE0000385; name: Interferon alpha/beta receptor 2; organism: Humans; known_action: yes; parent_key: DB00008.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 15; parent_key: DB00696.", + "id: BE0003788; name: Death-associated protein kinase 3; organism: Humans; known_action: unknown; position: 1; parent_key: DB07242.", + "id: BE0001164; name: Toll-like receptor 2; organism: Humans; known_action: yes; position: 7; parent_key: DB00210.", + "id: BE0000661; name: Interferon alpha/beta receptor 1; organism: Humans; known_action: yes; position: 2; parent_key: DB00011.", + "id: BE0001016; name: Rho-associated protein kinase 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB07876.", + "id: BE0000385; name: Interferon alpha/beta receptor 2; organism: Humans; known_action: unknown; parent_key: DB05472.", + "id: BE0003585; name: Neuronal acetylcholine receptor subunit alpha-3; organism: Humans; known_action: unknown; position: 2; parent_key: DB01227.", + "id: BE0000342; name: Alpha-2C adrenergic receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB01267.", + "id: BE0001100; name: Microtubule-associated protein 2; organism: Humans; known_action: yes; position: 10; parent_key: DB01229.", + "id: BE0003767; name: S-phase kinase-associated protein 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB06980.", + "id: BE0000385; name: Interferon alpha/beta receptor 2; organism: Humans; known_action: yes; parent_key: DB00022.", + "id: BE0000515; name: Melatonin receptor type 1A; organism: Humans; known_action: yes; parent_key: DB00980.", + "id: BE0009373; name: Skin epithelial cells; organism: Humans; known_action: yes; position: 1; parent_key: DB11185.", + "id: BE0000385; name: Interferon alpha/beta receptor 2; organism: Humans; known_action: yes; parent_key: DB00034." + ] + }, + { + "example_idx": 43, + "anchor_id": 18421819395433054625, + "positive_id": 2769859229762289646, + "join_paths": [ + [ + 7, + 10, + 0.251953125 + ], + [ + 7, + 25, + 0.2451171875 + ], + [ + 7, + 4, + 0.234375 + ], + [ + 7, + 37, + 0.2294921875 + ], + [ + 7, + 26, + 0.224609375 + ] + ], + "rows": [ + "BACKGROUND: Previous studies from our laboratory have demonstrated that in an animal model of acute cervical spinal cord injury (SCI), respiratory function can be restored by theophylline.", + "We also have shown that respiratory recovery occurs spontaneously after prolonged postinjury survival periods when a hemidiaphragm is paralyzed by an ipsilateral upper cervical (C2) spinal cord hemisection.", + "Theophylline mediates functional recovery by central nervous system adenosine A1 receptor antagonism; however, it is unclear whether adenosine receptors are altered after prolonged postinjury periods and whether theophylline can further enhance restored respiratory function that occurs spontaneously.", + "OBJECTIVE: To assess putative effects of systemic theophylline administration on further enhancing spontaneous respiratory muscle recovery 4 months after C2 hemisection in rats and to determine whether adenosine A1 receptor mRNA expression is altered in these animals.", + "METHODS: Electrophysiologic assessment of respiratory activity in the phrenic nerves was conducted in C2 hemisected rats 4 months after hemisection under standardized conditions.", + "Immediately thereafter, rats were killed and the cervical spinal cords were prepared for adenosine A1 receptor mRNA expression by in situ hybridization.", + "RESULTS: Spontaneous recovery of respiratory activity in the ipsilateral phrenic nerve was detected in a majority (15/20) of C2 hemisected animals and amounted to 44.06% +/- 2.38% when expressed as a percentage of activity in the homolateral phrenic nerve in noninjured animals.", + "At the optimal dosage used in the acute studies, theophylline (15 mg/kg) did not enhance, but rather unexpectedly blocked, recovered respiratory activity in 4 out of 5 animals tested.", + "At dosages of 5 mg/kg and 2.5 mg/kg, the drug blocked recovered respiratory activity in 3 out of 4 and 3 out of 5 animals tested, respectively.", + "Quantitative analysis of adenosine A1 receptor mRNA expression did not reveal a significant difference between experimental animals and sham-operated animals.", + "CONCLUSION: The blockade or attenuation of spontaneously recovered respiratory activity following theophylline administration cannot be attributed to changes in adenosine A1 receptors because there were no significant differences in adenosine A1 mRNA expression with sham-operated animals.", + "Lack of alteration in A1 mRNA expression 4 months after cervical SCI suggests that A1 receptor plasticity is not activated by chronic injury.", + "Obliteration of spontaneous recovery with theophylline most likely involves a separate unknown mechanism.", + "These findings suggest that there may be a limited therapeutic window for the clinical application of theophylline in SCI patients with respiratory deficits.", + "Theophylline may be more effective clinically in the acute phase of injury rather than in the chronic phase.", + "Animals\nDiaphragm\nDose-Response Relationship, Drug\nFemale\nFunctional Laterality\nGene Expression\nMotor Neurons\nNeuronal Plasticity\nPhosphodiesterase Inhibitors\nPhrenic Nerve\nRNA, Messenger\nRats\nRats, Sprague-Dawley\nReceptor, Adenosine A1\nRespiratory Paralysis\nSpinal Cord Injuries\nTheophylline" + ], + "sentences": [ + "name: Theophylline Elixir; ingredients: Theophylline; parent_key: DB00277.", + "name: Apo-theo ER; ingredients: Theophylline; parent_key: DB00277.", + "name: Theolair Tab 250mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Theolair SR Tab 500mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Theophylline; ingredients: Theophylline; parent_key: DB00277.", + "name: Quibron T SR Tab 300mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Slo-bid 300; ingredients: Theophylline; parent_key: DB00277.", + "name: A.H.c Cotton 100 Mask Soy Isoflavone; ingredients: Adenosine + Allantoin + Nicotinamide; parent_key: DB11100.", + "name: Theo-SR 300 Srt 300mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Plan36.5 Tranex 11 Plus; ingredients: Adenosine + Nicotinamide; parent_key: DB02701.", + "name: Theophylline (Anhydrous); ingredients: Theophylline; parent_key: DB00277.", + "name: Theophylline Extended Release; ingredients: Theophylline; parent_key: DB00277.", + "name: Theolair SR Tab 300mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Theochron Srt 100mg; ingredients: Theophylline; parent_key: DB00277.", + "name: PMS-theophylline Elixir; ingredients: Theophylline; parent_key: DB00277.", + "name: Quibron T/SR; ingredients: Theophylline; parent_key: DB00277.", + "name: Theolair; ingredients: Theophylline; parent_key: DB00277.", + "name: Elixir De Theophylline; ingredients: Theophylline; parent_key: DB00277.", + "name: Theolair SR Tab 200mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Uniphyl; ingredients: Theophylline; parent_key: DB00277.", + "name: Theo-dur 450 mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Theophylline Anhydrous; ingredients: Theophylline; parent_key: DB00277.", + "name: Theochron Srt 300mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Protecting Natural Shine Tone Up Sun Cushion Refull; ingredients: Adenosine + Nicotinamide + Titanium dioxide + Zinc oxide; parent_key: DB02701.", + "name: Theolair SR Tab 250mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Theophylline(Anhydrous); ingredients: Theophylline; parent_key: DB00277.", + "name: Theophylline in Dextrose; ingredients: Theophylline; parent_key: DB00277.", + "name: Theolair Tab 125mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Moisture Bound; ingredients: Adenosine + Ceramide NP + Nicotinamide + Tremella fuciformis whole; parent_key: DB14359.", + "name: ELCURE AOUT Rose; ingredients: Adenosine; parent_key: DB00640.", + "name: Theo-dur 100 mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Skinfood Miracle Food 10 Solu Tion; ingredients: Adenosine + Glycerin + Nicotinamide; parent_key: DB02701.", + "name: Slo-bid 50; ingredients: Theophylline; parent_key: DB00277.", + "name: Protective Base Sun for Oily Skin; ingredients: Adenosine + Nicotinamide + Titanium dioxide + Zinc oxide; parent_key: DB09536.", + "name: Theo-dur 200 mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Theophylline Elx; ingredients: Theophylline; parent_key: DB00277.", + "name: Hello Care Pore and Sebum Ampoule Mask; ingredients: Adenosine + Nicotinamide; parent_key: DB00640.", + "name: Theophylline 80mg/15ml; ingredients: Theophylline; parent_key: DB00277.", + "name: Theo-24; ingredients: Theophylline; parent_key: DB00277.", + "name: Quibron-T; ingredients: Theophylline; parent_key: DB00277.", + "name: Teva-theophylline SR; ingredients: Theophylline; parent_key: DB00277.", + "name: Theo-dur 300 mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Elixophyllin; ingredients: Theophylline; parent_key: DB00277.", + "name: Theo ER; ingredients: Theophylline; parent_key: DB00277.", + "name: Slo-bid 100; ingredients: Theophylline; parent_key: DB00277.", + "name: Slo-bid 200; ingredients: Theophylline; parent_key: DB00277.", + "name: Birds Nest Forever Young Multi Care Lifting; ingredients: Adenosine + Nicotinamide; parent_key: DB02701.", + "name: Theochron Srt 200mg; ingredients: Theophylline; parent_key: DB00277.", + "name: Aa-theo LA; ingredients: Theophylline; parent_key: DB00277.", + "name: Super Amazing Revolution For Secret; ingredients: Adenosine; parent_key: DB00640." + ] + }, + { + "example_idx": 44, + "anchor_id": 5617043313163895977, + "positive_id": 14199596712502649809, + "join_paths": [ + [ + 0, + 0, + 0.267578125 + ], + [ + 0, + 41, + 0.1513671875 + ], + [ + 0, + 44, + 0.150390625 + ] + ], + "rows": [ + "Digoxin, which is one of the most commonly prescribed drugs for the treatment of heart failure, is mainly eliminated from the circulation by the kidney.", + "P-glycoprotein is well characterized as a digoxin pump at the apical membrane of the nephron.", + "However, little is known about the transport mechanism at the basolateral membrane.", + "We have isolated an organic anion transporter (OATP4C1) from human kidney.", + "Human OATP4C1 is the first member of the organic anion transporting polypeptide (OATP) family expressed in human kidney.", + "The isolated cDNA encodes a polypeptide of 724 aa with 12 transmembrane domains.", + "The genomic organization consists of 13 exons located on chromosome 5q21.", + "Its rat counterpart, Oatp4c1, is also isolated from rat kidney.", + "Human OATP4C1 transports cardiac glycosides (digoxin, K(m) = 7.8 microM and ouabain, K(m) = 0.38 microM), thyroid hormone (triiodothyronine, K(m) = 5.9 microM and thyroxine), cAMP, and methotrexate in a sodium-independent manner.", + "Rat Oatp4c1 also transports digoxin (K(m) = 8.0 microM) and triiodothyronine (K(m) = 1.9 microM).", + "Immunohistochemical analysis reveals that rat Oatp4c1 protein is localized at the basolateral membrane of the proximal tubule cell in the kidney.", + "These data suggest that human OATP4C1/rat Oatp4c1 might be a first step of the transport pathway of digoxin and various compounds into urine in the kidney.", + "Amino Acid Sequence\nAnimals\nBase Sequence\nCell Line\nCloning, Molecular\nDNA, Complementary\nDigoxin\nDogs\nFemale\nHumans\nKidney\nKinetics\nMale\nMolecular Sequence Data\nOrganic Anion Transporters\nPhylogeny\nRNA, Messenger\nRats\nRecombinant Proteins\nRenal Insufficiency\nSequence Homology, Amino Acid\nTissue Distribution\nTransfection" + ], + "sentences": [ + "name: Digox; ingredients: Digoxin; parent_key: DB00390.", + "name: Multicaps; ingredients: Ascorbic acid + Biotin + Calcium + Cholecalciferol + Choline + Chromium + Cyanocobalamin + Folic acid + Inositol + Magnesium + Manganese + Niacin + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Thiamine + Vitamin A + Vitamin E + Zinc; parent_key: DB00115.", + "name: Raplixa; ingredients: Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: Insulatard; ingredients: Insulin human; parent_key: DB00030.", + "name: Acid Concentrate D12251; ingredients: Acetic acid + Calcium chloride + Sodium chloride; parent_key: DB03166.", + "name: Novolin R; ingredients: Insulin human; parent_key: DB00030.", + "name: Humulin 10/90 Inj; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Haemosol H-223; ingredients: Acetic acid + Calcium chloride + Dextrose, unspecified form + Magnesium chloride + Potassium chloride + Sodium chloride; parent_key: DB01164.", + "name: Utac; ingredients: Methenamine + Sodium phosphate, monobasic; parent_key: DB06799.", + "name: Humulin 70/30 KwikPen; ingredients: Insulin human; parent_key: DB00030.", + "name: Insulatard Penfill; ingredients: Insulin human; parent_key: DB00030.", + "name: Novolinset Ge Toronto Inj Liq 100u/ml; ingredients: Insulin human; parent_key: DB00030.", + "name: Albuked; ingredients: Albumin human; parent_key: DB00062.", + "name: Pinto Bean; ingredients: Kidney bean; parent_key: DB10639.", + "name: Novolin 70/30; ingredients: Insulin human; parent_key: DB00030.", + "name: Diluent for Allergenic Extract Sterile Albumin Saline With Phenol; ingredients: Albumin human; parent_key: DB00062.", + "name: Insulin Human Winthrop Rapid; ingredients: Insulin human; parent_key: DB00030.", + "name: Vitamin C Tab 500 mg; ingredients: Ascorbic acid; parent_key: DB00126.", + "name: Afrezza; ingredients: Insulin human; parent_key: DB00030.", + "name: Actrapid Penfill; ingredients: Insulin human; parent_key: DB00030.", + "name: Actrapid; ingredients: Insulin human; parent_key: DB00030.", + "name: EVICEL Fibrin Sealant (Human); ingredients: Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: Humulin 40/60 Inj; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Dothelle DHA; ingredients: Ascorbic acid + Biotin + Cupric sulfate + Cyanocobalamin + Doconexent + Ferrous fumarate + Folic acid + Icosapent + Iron + Magnesium sulfate + Niacin + Omega-3 fatty acids + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Zinc sulfate, unspecified form; parent_key: DB00140.", + "name: Buminate 5%; ingredients: Albumin human; parent_key: DB00062.", + "name: Insuman Basal; ingredients: Insulin human; parent_key: DB00030.", + "name: Entuzity Kwikpen; ingredients: Insulin human; parent_key: DB00030.", + "name: Lanoxin Tab 0.25mg; ingredients: Digoxin; parent_key: DB00390.", + "name: Humulin 10/90 Cartridge; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Insulin Human Winthrop Comb 15; ingredients: Insulin human; parent_key: DB00030.", + "name: Helicobacter Test Infai for Children Of The Age 3-11; ingredients: Urea C-13; parent_key: DB09510.", + "name: Evarrest; ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222.", + "name: Actraphane 30 Innolet; ingredients: Insulin human; parent_key: DB00030.", + "name: Acid Concentrate Bp Rz267c; ingredients: Acetic acid + Calcium chloride + Magnesium chloride + Potassium chloride + Sodium chloride; parent_key: DB00761.", + "name: White Kidney Beans; ingredients: Kidney bean; parent_key: DB10639.", + "name: Humulin 50/50 Cartridge; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Albunex; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuminex; ingredients: Albumin human; parent_key: DB00062.", + "name: Sodium Bicarbonate Injection 75mg/ml; ingredients: Sodium bicarbonate; parent_key: DB01390.", + "name: TachoSil; ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222.", + "name: Novolinset Ge 30/70 Inj Sus; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Lanoxin Inj 0.25mg/ml; ingredients: Digoxin; parent_key: DB00390.", + "name: Pranactin-Citric; ingredients: Urea C-13; parent_key: DB09510.", + "name: Insulin Human Winthrop Comb 30; ingredients: Insulin human; parent_key: DB00030.", + "name: Lanoxin Tab 0.0625mg; ingredients: Digoxin; parent_key: DB00390.", + "name: Humulin U; ingredients: Insulin human; parent_key: DB00030.", + "name: Humalog 70/30; ingredients: Insulin human; parent_key: DB00030.", + "name: SUEROLYTE Oral Electrolyte Solution Bubbe Gum Flavor; ingredients: D-glucose + Potassium citrate + Sodium chloride + Sodium chlorite + Zinc; parent_key: DB01914.", + "name: Evicel; ingredients: Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: TL-Fluorivite; ingredients: Ascorbic acid + Biotin + Copper + Cyanocobalamin + Folic acid + Iron + Magnesium + Niacin + Pantothenic acid + Pyridoxine + Riboflavin + Sodium fluoride + Thiamine + Vitamin A + Vitamin D + Vitamin E + Zinc; parent_key: DB00163." + ] + }, + { + "example_idx": 45, + "anchor_id": 15613645375438446170, + "positive_id": 14312421464443551827, + "join_paths": [ + [ + 9, + 4, + 0.1865234375 + ], + [ + 9, + 21, + 0.18359375 + ], + [ + 9, + 10, + 0.1826171875 + ], + [ + 9, + 23, + 0.181640625 + ], + [ + 9, + 42, + 0.181640625 + ] + ], + "rows": [ + "The detection of clinical isolates with decreased fluoroquinolone susceptibilities and a resistance mechanism is of epidemiological and clinical interest.", + "We studied the susceptibilities of 62 clinical isolates and 2 American Type Culture Collection reference strains of Haemophilus influenzae to ciprofloxacin, levofloxacin, moxifloxacin, and nalidixic acid by the microdilution and disk diffusion methods.", + "The ciprofloxacin MICs for 34 of the isolates were >/=0.12 micro g/ml (range, 0.12 to 32 micro g/ml), and the ciprofloxacin MICs for 28 matched control isolates were /=0.5 micro g/ml and the vast majority of those for which nalidixic acid MICs were >/=32 micro g/ml exhibited amino acid changes in GyrA and ParC.", + "Nalidixic acid and the other three fluoroquinolones studied could be used to screen H. influenzae isolates for the detection of decreased susceptibilities to quinolones due to the acquisition of two amino acid changes in the QRDRs of GyrA and ParC (sensitivity, >95%; specificity, >80%).", + "Aza Compounds\nBase Sequence\nCiprofloxacin\nDNA Gyrase\nDNA Primers\nDNA Topoisomerase IV\nFluoroquinolones\nHaemophilus Infections\nHaemophilus influenzae\nHumans\nLevofloxacin\nMicrobial Sensitivity Tests\nMoxifloxacin\nNalidixic Acid\nOfloxacin\nPolymerase Chain Reaction\nQuinolines" + ], + "sentences": [ + "id: BE0003836; name: Ig kappa chain C region; organism: Humans; known_action: unknown; position: 1; parent_key: DB07882.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB04571.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 2; parent_key: DB04572.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01103.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00442.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00276.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 2; parent_key: DB00709.", + "id: BE0003851; name: Reaction center protein L chain; organism: Rhodopseudomonas viridis; known_action: unknown; position: 17; parent_key: DB08690.", + "id: BE0004796; name: DNA; organism: Humans; known_action: no; parent_key: DB00693.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB03148.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB09348.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB00131.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; position: 2; parent_key: DB00126.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00515.", + "id: BE0000419; name: Solute carrier family 12 member 3; organism: Humans; known_action: yes; position: 2; parent_key: DB00808.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 6; parent_key: DB01030.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00385.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; position: 1; parent_key: DB02842.", + "id: BE0000642; name: 72 kDa type IV collagenase; organism: Humans; known_action: unknown; position: 2; parent_key: DB01197.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01206.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB05129.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00441.", + "id: BE0000381; name: Gamma-aminobutyric acid receptor subunit alpha-2; organism: Humans; known_action: yes; position: 2; parent_key: DB01351.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 4; parent_key: DB01041.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00531.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04996.", + "id: BE0003595; name: Gamma-aminobutyric acid receptor subunit epsilon; organism: Humans; known_action: yes; position: 12; parent_key: DB01567.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01265.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00997.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 6; parent_key: DB09327.", + "id: BE0000478; name: Gamma-aminobutyric acid receptor subunit alpha-4; organism: Humans; known_action: yes; position: 3; parent_key: DB01353.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB00536.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB00173.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 2; parent_key: DB01004.", + "id: BE0001367; name: Tubulin beta-4B chain; organism: Humans; known_action: unknown; position: 35; parent_key: DB12695.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00853.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB05706.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00428.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01280.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 5; parent_key: DB00544.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01610.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00851.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00911.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB04967.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB00738.", + "id: BE0000430; name: Voltage-dependent L-type calcium channel subunit alpha-1C; organism: Humans; known_action: yes; position: 1; parent_key: DB00308.", + "id: BE0001142; name: Geranylgeranyl transferase type-1 subunit beta; organism: Humans; known_action: unknown; position: 2; parent_key: DB07841.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00352.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB01702.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01611." + ] + }, + { + "example_idx": 46, + "anchor_id": 15969007205223000435, + "positive_id": 997016382196470320, + "join_paths": [ + [ + 5, + 45, + 0.1865234375 + ], + [ + 5, + 10, + 0.185546875 + ], + [ + 5, + 13, + 0.1845703125 + ], + [ + 4, + 45, + 0.1728515625 + ], + [ + 5, + 14, + 0.16015625 + ] + ], + "rows": [ + "Receptor-mediated endocytosis plays an important role in accumulation of aminoglycosides in renal proximal tubule.", + "To prevent aminoglycoside-induced nephrotoxicity following concentrated accumulation of gentamicin in the kidney, effect of cationic proteins and their peptide fragments, which could inhibit gentamicin binding to its binding receptor(s), was investigated.", + "Among several substrates for megalin, an endocytic receptor responsible for renal accumulation of aminoglycosides, cytochrome c potently inhibited gentamicin accumulation in renal cortex.", + "Concentration-dependent inhibition by cytochrome c on gentamicin uptake was also observed in OK kidney epithelial cells expressing megalin.", + "In addition, gentamicin-induced increase in urinary excretion of N-acetyl-beta-d-glucosaminidase (NAG), a marker of renal tubular damage, was significantly reduced by cytochrome c. We next attempted to find a peptide fragment with lower molecular size showing inhibitory effect on gentamicin uptake.", + "Cyto79-88 inhibited gentamicin uptake in OK cells, but had little effect on renal accumulation of gentamicin in mice in vivo.", + "On one hand, a peptide fragment of neural Wiskott-Aldrich syndrome protein (N-WASP), which interacts with acidic phospholipids like aminoglycosides, inhibited gentamicin accumulation not only in OK cells but also in mouse kidney.", + "These results show that substrates and/or their peptide fragments for aminoglycoside binding receptor such as megalin might be useful for preventing aminoglycoside-induced nephrotoxicity.", + "Acetylglucosaminidase\nAminoglycosides\nAnimals\nAprotinin\nBinding Sites\nCells, Cultured\nCytochromes c\nDehydration\nDisease Models, Animal\nDose-Response Relationship, Drug\nDrug Delivery Systems\nDrug Evaluation, Preclinical\nDrug Therapy, Combination\nEndocytosis\nGentamicins\nJapan\nKidney Cortex\nKidney Tubules, Proximal\nLow Density Lipoprotein Receptor-Related Protein-2\nMale\nMice\nMice, Inbred Strains\nMuramidase\nNerve Tissue Proteins\nPeptide Fragments\nPeptides\nRats\nRats, Wistar\nReceptors, Drug\nSpecies Specificity\nTissue Distribution\nTritium" + ], + "sentences": [ + "name: Dom-gentamicin-betamethasone; ingredients: Betamethasone + Gentamicin; parent_key: DB00443.", + "name: Gantrisin; ingredients: Acetyl sulfisoxazole; parent_key: DB14033.", + "name: Gentacidin Oph Soln 3mg/ml; ingredients: Gentamicin; parent_key: DB00798.", + "name: HUCORD HSCM-100 Ampoule; ingredients: Insulin-like growth factor II; parent_key: DB14472.", + "name: Gentrasul Liq 3mg/ml; ingredients: Gentamicin; parent_key: DB00798.", + "name: Pred-G; ingredients: Gentamicin + Prednisolone acetate; parent_key: DB15566.", + "name: Garasone Ophthalmic Ointment; ingredients: Betamethasone + Gentamicin; parent_key: DB00798.", + "name: Prenatal Formula Tab; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Choline + Chromium + Copper + Cyanocobalamin + D-alpha-Tocopherol acetate + Folic acid + Inositol + Iron + Magnesium + Manganese + Molybdenum + Niacin + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Racemethionine + Riboflavin + Selenium + Thiamine + Vanadium + Vitamin A + Zinc; parent_key: DB14500.", + "name: Ceprotin; ingredients: Protein C; parent_key: DB11312.", + "name: Gentamicin Sulphate Injection USP-10mg/ml; ingredients: Gentamicin; parent_key: DB00798.", + "name: Gentamicin sulfate; ingredients: Gentamicin; parent_key: DB00798.", + "name: Dom-gentamicin-betamethasone; ingredients: Betamethasone + Gentamicin; parent_key: DB00798.", + "name: PMS-gentamicin Ointment 1mg/gm; ingredients: Gentamicin; parent_key: DB00798.", + "name: Gentamicin Sulfate in Sodium Chloride; ingredients: Gentamicin; parent_key: DB00798.", + "name: Gentamicin Injection USP; ingredients: Gentamicin; parent_key: DB00798.", + "name: Ratio-gentamicin; ingredients: Gentamicin; parent_key: DB00798.", + "name: HydroGold 9; ingredients: Acetyl hexapeptide-3 + Adenosine + Allantoin + Benzoic acid + Butylene glycol + Castor oil + Dimethicone + Glycerin + Gold + Nicotinamide + Phenoxyethanol + Potassium chloride + Titanium dioxide + Xanthan gum; parent_key: DB11113.", + "name: Cidomycin Inj 10mg/ml; ingredients: Gentamicin; parent_key: DB00798.", + "name: Kidney Bean; ingredients: Kidney bean; parent_key: DB10639.", + "name: Garatec Otic Dps 5mg/ml; ingredients: Gentamicin; parent_key: DB00798.", + "name: Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl; ingredients: Acetyl sulfisoxazole + Erythromycin; parent_key: DB00199.", + "name: Garasone Ophthalmic and Otic Solution; ingredients: Betamethasone + Gentamicin; parent_key: DB00798.", + "name: Gentamicin Sulfate Cream 0.1%; ingredients: Gentamicin; parent_key: DB00798.", + "name: Sandoz Pentasone; ingredients: Betamethasone + Gentamicin; parent_key: DB00798.", + "name: NataChew; ingredients: Ascorbic acid + Beta carotene + Cholecalciferol + Cyanocobalamin + D-alpha-Tocopherol acetate + Folic acid + Iron + Nicotinamide + Pyridoxine + Riboflavin + Thiamine; parent_key: DB00140.", + "name: Master Key Multi Vitamin Multi Mineral Formula 2; ingredients: alpha-Tocopherol succinate + Ascorbic acid + Beta carotene + Biotin + Choline + Chromium + Cyanocobalamin + Folic acid + Inositol + Iodine + Magnesium + Manganese + Niacin + Nicotinamide + Pantothenic acid + Potassium + Pyridoxine + Racemethionine + Riboflavin + Selenium + Thiamine + Vitamin A + Zinc; parent_key: DB11136.", + "name: Sandoz Pentasone; ingredients: Betamethasone + Gentamicin; parent_key: DB00443.", + "name: 10% Travamulsion Liq IV; ingredients: Egg phospholipids + Soybean oil; parent_key: DB09422.", + "name: Pred-G; ingredients: Gentamicin + Prednisolone acetate; parent_key: DB00798.", + "name: Liposyn III; ingredients: Egg phospholipids + Glycerin + Soybean oil; parent_key: DB09422.", + "name: Vinate AZ; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Folic acid + Iron + Magnesium oxide + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB00169.", + "name: Liposyn III; ingredients: Egg phospholipids + Glycerin + Soybean oil; parent_key: DB09462.", + "name: Betamycin Ophthalmic/otic Solution; ingredients: Betamethasone + Gentamicin; parent_key: DB00798.", + "name: Cidomycin Inj Pediatric 10mg; ingredients: Gentamicin; parent_key: DB00798.", + "name: Gentak; ingredients: Gentamicin; parent_key: DB00798.", + "name: Diprogen Cream; ingredients: Betamethasone + Gentamicin; parent_key: DB00443.", + "name: Vyo Cylate - Pwr; ingredients: Beta carotene + Biotin + Calcium + Calcium ascorbate + Chromium + Copper + Cyanocobalamin + DL-alpha tocopheryl acetate + Ferrous fumarate + Folic acid + Magnesium + Niacin + Pantothenic acid + Phosphorus + Potassium + Potassium Iodide + Pyridoxine + Riboflavin + Selenious acid + Thiamine + Vitamin D + Zinc; parent_key: DB14491.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB13306.", + "name: Gentamicin Sulfate In Nacl 0.9% Inj; ingredients: Gentamicin + Sodium chloride; parent_key: DB09153.", + "name: Diprogen Ointment; ingredients: Betamethasone + Gentamicin; parent_key: DB00798.", + "name: Garamycin Inj 40mg/ml; ingredients: Gentamicin; parent_key: DB00798.", + "name: Celestone-G; ingredients: Betamethasone + Gentamicin; parent_key: DB00443.", + "name: Children's Chewable Vit and Min Tab; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Choline + Cyanocobalamin + Folic acid + Inositol + Iron + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Potassium + Pyridoxine + Riboflavin + Thiamine + Vitamin E + Zinc; parent_key: DB06755.", + "name: Garamycin Otic Drops 0.3%; ingredients: Gentamicin; parent_key: DB00798.", + "name: Trinatal Rx 1; ingredients: Acetate + Ascorbic acid + Beta carotene + Biotin + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Ferrous fumarate + Folic acid + Magnesium oxide + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB00152.", + "name: Gentamicin(e); ingredients: Gentamicin; parent_key: DB00798.", + "name: Garasone Ophthalmic Ointment; ingredients: Betamethasone + Gentamicin; parent_key: DB00443.", + "name: Extra Once A Day; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Choline + Chromium + Copper + Cyanocobalamin + Ferrous fumarate + Folic acid + Inositol + Magnesium + Manganese + Molybdenum + Niacin + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Racemethionine + Riboflavin + Selenium + Thiamine + Vanadium + Vitamin A + Vitamin E + Zinc; parent_key: DB13178.", + "name: Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl; ingredients: Acetyl sulfisoxazole + Erythromycin; parent_key: DB14033.", + "name: Garamycin Inj 10mg/ml Pediatric; ingredients: Gentamicin; parent_key: DB00798." + ] + }, + { + "example_idx": 47, + "anchor_id": 3277137801490637834, + "positive_id": 7903318728546022651, + "join_paths": [ + [ + 8, + 46, + 0.26953125 + ], + [ + 9, + 46, + 0.263671875 + ], + [ + 8, + 11, + 0.26171875 + ], + [ + 8, + 20, + 0.26171875 + ], + [ + 9, + 20, + 0.26171875 + ] + ], + "rows": [ + "BACKGROUND: The antiestrogen tamoxifen has potent activity against estrogen receptor-positive breast cancer, but two nonsteroidal aromatase inhibitors, letrozole and anastrozole, show considerable advantages over tamoxifen with respect to patient survival and tolerability.", + "To determine the optimal way to use letrozole and tamoxifen, we studied their effects on a breast tumor xenograft model, MCF-7Ca, that is responsive to both antiestrogens and aromatase inhibitors.", + "METHODS: Female ovariectomized BALB/c athymic nude mice carrying xenograft tumors were treated daily subcutaneously with one of the following first-line therapies for varying durations: no drug (control), tamoxifen (100 microg/day) alone, letrozole (10 microg/day) alone, both drugs at the same time, or alternating 4-week courses of each drug (beginning with a course of tamoxifen or beginning with a course of letrozole).", + "Tumor volumes and weights were estimated using linear mixed-effects models.", + "The time to tumor doubling was calculated, and tumor weights in the treatment groups were compared, with adjustments for multiple comparisons being made with either Tukey's or Dunnett's procedure.", + "Second-line therapies (with tamoxifen, letrozole, or fulvestrant) were initiated when tumors doubled in size under first-line therapies.", + "All statistical tests were two-sided.", + "RESULTS: The times for doubling of tumor volume were as follows: control, 3-4 weeks; tamoxifen alone, 16 weeks; tamoxifen alternating with letrozole, 17-18 weeks; tamoxifen plus letrozole, 18 weeks; letrozole alternating with tamoxifen, 22 weeks; letrozole alone, 34 weeks.", + "First-line treatment with letrozole was superior to treatment with tamoxifen alone or with the two drugs combined (at week 16, both P<.001).", + "Alternating tamoxifen and letrozole and alternating letrozole and tamoxifen were also not as effective as letrozole alone (at week 16, P =.002 and P<.001, respectively).", + "Tumors progressing on tamoxifen remained sensitive to second-line therapy with letrozole compared with those remaining on tamoxifen at the end of treatment (week 28, P<.001), whereas tumors progressing on letrozole were unaffected by second-line treatment with the antiestrogens tamoxifen or fulvestrant.", + "CONCLUSIONS: First-line letrozole therapy extends time for tumor progression in this model relative to the other treatment regimens tested.", + "However, further studies are needed to determine the most effective second-line therapy for tumors that progress on letrozole.", + "Animals\nAntineoplastic Combined Chemotherapy Protocols\nAromatase Inhibitors\nBreast Neoplasms\nDisease Models, Animal\nDisease Progression\nDrug Administration Schedule\nEnzyme Inhibitors\nEstrogen Receptor Modulators\nFemale\nHumans\nLetrozole\nLinear Models\nMice\nMice, Inbred BALB C\nMice, Nude\nNeoplasms, Hormone-Dependent\nNitriles\nOrgan Size\nOvariectomy\nTamoxifen\nTransplantation, Heterologous\nTriazoles\nUterus" + ], + "sentences": [ + "name: Med-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Nolvadex-D Tab 20mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Ccp-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Apo-tamox Tab 20mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Ipg-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Accel-letrozole Tablets USP; ingredients: Letrozole; parent_key: DB01006.", + "name: Co Letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Menveo; ingredients: Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine + Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13887.", + "name: Fluarix Quadrivalent 2018/2019; ingredients: Influenza A virus A/Singapore/gp1908/2015 IVR-180 (H1N1) antigen (formaldehyde inactivated) + Influenza A virus A/Singapore/INFIMH-16-0019/2016 NIB-104 (H3N2) antigen (formaldehyde inactivated) + Influenza B virus B/Maryland/15/2016 BX-69A antigen (formaldehyde inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (formaldehyde inactivated); parent_key: DB14558.", + "name: Van-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Ran-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Letrozole Tablets; ingredients: Letrozole; parent_key: DB01006.", + "name: Vasolex; ingredients: Balsam of Peru + Castor oil + Trypsin; parent_key: DB11482.", + "name: Auro-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Zinda-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Stason-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Femara; ingredients: Letrozole; parent_key: DB01006.", + "name: Nolvadex; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Mar-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Medical Provider Single Use EZ Flu Shot Kit; ingredients: Influenza A virus A/Christchurch/16/2010 NIB-74 (H1N1) antigen (propiolactone inactivated) + Influenza A virus A/Victoria/361/2011 IVR-165 (H3N2) antigen (propiolactone inactivated) + Influenza B virus B/Hubei-Wujiagang/158/2009 BX-39 antigen (propiolactone inactivated); parent_key: DB02325.", + "name: Sandoz Letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Nat-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Teva-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Tamoxifen Citrate; ingredients: Tamoxifen; parent_key: DB00675.", + "name: PMS-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Ag-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Fluvirin; ingredients: Influenza A virus A/Christchurch/16/2010 NIB-74 (H1N1) antigen (propiolactone inactivated) + Influenza A virus A/Hong Kong/4801/2014 X-263B (H3N2) antigen (propiolactone inactivated) + Influenza B virus B/Brisbane/60/2008 antigen (propiolactone inactivated); parent_key: DB10781.", + "name: Tamone Tab 20mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Femara 2.5mg; ingredients: Letrozole; parent_key: DB01006.", + "name: Fluarix Quadrivalent 2014/2015; ingredients: Influenza A virus A/Christchurch/16/2010 NIB-74XP (H1N1) antigen (formaldehyde inactivated) + Influenza A virus A/Texas/50/2012 X-223A (H3N2) antigen (formaldehyde inactivated) + Influenza B virus B/Brisbane/60/2008 antigen (formaldehyde inactivated) + Influenza B virus B/Massachusetts/2/2012 BX-51B antigen (formaldehyde inactivated); parent_key: DB10996.", + "name: Mylan-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Dom-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Ach-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Jamp-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Bio-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Tamone Tab 10mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Acam2000; ingredients: Vaccinia virus strain new york city board of health live antigen; parent_key: DB14711.", + "name: Tamoplex Tab 10mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Myl-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Soltamox; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Letrozole Sun; ingredients: Letrozole; parent_key: DB01006.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB13743.", + "name: PHL-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Teva-tamoxifen; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Apo-letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Gardasil; ingredients: Human papillomavirus type 11 L1 capsid protein antigen + Human papillomavirus type 16 L1 capsid protein antigen + Human papillomavirus type 18 L1 capsid protein antigen + Human papillomavirus type 6 L1 capsid protein antigen; parent_key: DB10302.", + "name: Letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Fluarix 2014/2015; ingredients: Influenza A virus A/Christchurch/16/2010 NIB-74XP (H1N1) antigen (formaldehyde inactivated) + Influenza A virus A/Texas/50/2012 X-223A (H3N2) antigen (formaldehyde inactivated) + Influenza B virus B/Massachusetts/2/2012 BX-51B antigen (formaldehyde inactivated); parent_key: DB10996.", + "name: Apo-tamox Tab 10mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Riva-letrozole; ingredients: Letrozole; parent_key: DB01006." + ] + }, + { + "example_idx": 48, + "anchor_id": 16698423439417527876, + "positive_id": 17251708000166894830, + "join_paths": [ + [ + 0, + 33, + 0.19921875 + ], + [ + 9, + 33, + 0.1689453125 + ], + [ + 10, + 39, + 0.1640625 + ], + [ + 10, + 1, + 0.16015625 + ], + [ + 10, + 14, + 0.1572265625 + ] + ], + "rows": [ + "P-glycoprotein (P-gp) is a 170-kDa membrane protein and the gene product of the multiple drug resistance (MDR1 or ABCB1) gene.", + "It constitutes an important part of the blood-brain barrier and actively exports a number of molecules across the blood-brain barrier back into the vascular space, subsequently reducing central nervous system (CNS) bioavailability of these substances.", + "The aim of the present study was to investigate the pharmacokinetics of amitriptyline and its metabolites in P-gp (also called mdr1ab or abcb1ab) knockout mice and controls after a long-term adminstration for 10 days.", + "Knockout mice and controls received s.c. injections of amitriptyline (10 microg/g bodyweight) twice daily for 10 days.", + "After 10 days, the animals were sacrificed and the concentrations of amitriptyline and nortriptyline and both their E-10-OH and Z-10-OH metabolites were measured with high-performance liquid chromatography in the cerebrum, plasma, spleen, kidney, testes, lung, liver, muscle and fat.", + "Except for amitriptyline, the brain concentrations of all other examined substances were significantly higher in the P-gp knockout mice.", + "Compared to controls, concentrations of nortriptyline were 2.6-fold higher, E-10-OH-nortriptyline 10-fold higher, Z-10-OH-nortriptyline seven-fold higher, E-10-OH-amitriptyline two-fold higher and Z-10-OH-amitriptyline five-fold higher.", + "The present study confirms that P-gp plays an important role in the interaction between CNS drugs and the blood-brain barrier.", + "Without P-gp at the blood-brain barrier, the brain concentrations of the substances were up to 10-fold higher, showing that P-gp plays an active role in exporting CNS drugs out of the brain.", + "Recent clinical studies showing different side-effects in patients with P-gp polymorphisms confirm the clinical importance of these findings.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAmitriptyline\nAnimals\nAntidepressive Agents, Tricyclic\nBlood-Brain Barrier\nBrain\nChromatography, High Pressure Liquid\nDrug Administration Schedule\nInjections, Subcutaneous\nMale\nMice\nMice, Knockout\nNortriptyline\nTissue Distribution" + ], + "sentences": [ + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 2; parent_key: DB01235.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB01051.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB03839.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00133.", + "id: BE0001069; name: Canalicular multispecific organic anion transporter 1; organism: Humans; known_action: unknown; position: 10; parent_key: DB00564.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 0; parent_key: DB00398.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 3; parent_key: DB00151.", + "id: BE0001204; name: Equilibrative nucleoside transporter 1; organism: Humans; known_action: unknown; position: 4; parent_key: DB00943.", + "id: BE0009899; name: Zinc transporter 10; organism: Humans; known_action: unknown; position: 113; parent_key: DB14548.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 2; parent_key: DB00135.", + "id: BE0009810; name: Solute carrier family 43 member 3; organism: Humans; known_action: unknown; position: 15; parent_key: DB00993.", + "id: BE0004710; name: Solute carrier family 10 member 6; organism: Humans; known_action: unknown; position: 9; parent_key: DB05804.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00123.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00128.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 16; parent_key: DB13943.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00174.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00149.", + "id: BE0004710; name: Solute carrier family 10 member 6; organism: Humans; known_action: unknown; position: 1; parent_key: DB02789.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 63; parent_key: DB00142.", + "id: BE0003657; name: Multidrug and toxin extrusion protein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB09343.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00586.", + "id: BE0005220; name: Solute carrier family 2, facilitated glucose transporter member 10; organism: Humans; known_action: unknown; position: 11; parent_key: DB09341.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB03107.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 2; parent_key: DB00125.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 12; parent_key: DB00503.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 2; parent_key: DB00150.", + "id: BE0003649; name: High affinity copper uptake protein 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB00958.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB01017.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB01746.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 9; parent_key: DB00279.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB15233.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 25; parent_key: DB00563.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00117.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB01203.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 21; parent_key: DB00286.", + "id: BE0005220; name: Solute carrier family 2, facilitated glucose transporter member 10; organism: Humans; known_action: no; position: 12; parent_key: DB01914.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB01786.", + "id: BE0003652; name: Solute carrier family 22 member 10; organism: Humans; known_action: unknown; position: 14; parent_key: DB01032.", + "id: BE0003641; name: Multidrug resistance protein 3; organism: Humans; known_action: unknown; position: 4; parent_key: DB06207.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: yes; position: 4; parent_key: DB08931.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00134.", + "id: BE0001066; name: Solute carrier family 22 member 6; organism: Humans; known_action: unknown; position: 3; parent_key: DB00493.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00160.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB00843.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 4; parent_key: DB04398.", + "id: BE0005220; name: Solute carrier family 2, facilitated glucose transporter member 10; organism: Humans; known_action: yes; position: 11; parent_key: DB09502.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: no; position: 1; parent_key: DB13092.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB01685.", + "id: BE0003641; name: Multidrug resistance protein 3; organism: Humans; known_action: unknown; position: 2; parent_key: DB06414.", + "id: BE0003654; name: Monocarboxylate transporter 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB00167." + ] + }, + { + "example_idx": 49, + "anchor_id": 14012086452689954889, + "positive_id": 4289035254622096538, + "join_paths": [ + [ + 14, + 15, + 0.3671875 + ], + [ + 14, + 19, + 0.361328125 + ], + [ + 14, + 32, + 0.35546875 + ], + [ + 14, + 3, + 0.34765625 + ], + [ + 14, + 39, + 0.34765625 + ] + ], + "rows": [ + "AIM: To investigate the remodeling of mesenteric artery and the expression of TGF-beta1, c-Jun in mesenteric artery and effects of imidapril and irbesartan on the remodeling in spontaneously hypertensive rats (SHR).", + "METHODS: Thirty SHR (male/female, 21/9), aged 13 wk, were randomly divided into 3 groups (7 male rats and 3 female rats each group): SHR group, imidapril group (imidapril 3 mg/kg.d was given in drinking water for 14 wk), and irbesartan group (irbesartan 50 mg/kg.d was given in drinking water foe 14 wk).", + "Ten homogeneous Wistar Kyoto rats, 5 males and 5 females, weighing 206+/-49 g, were selected as normal control group (WKY group).", + "Systolic pressure was measured on d 1, 2, 4, 6, 8, 10, 12 and 14 during the experiment and the rats were killed at the end of the experiment.", + "Angiotensin II (Ang II) level in plasma and mesenteric arteries was measured by radioimmunoassay.", + "The morphology of the secondary branches of mesenteric artery were examined by light microscopy and electron microscopy.", + "Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of transforming growth factor TGF-beta1 and c-Jun mRNA.", + "RESULTS: Compared with imidapril group and irbesartan group, the blood pressure was remarkably increased in SHR group.", + "Ang II level in plasma and mesenteric arteries in SHR group was the same or lower than that in WKY group, and was higher in irbesartan group and lower in imidapril group.", + "The remodeling of mesenteric arteries in SHR group was mostly obvious among the 4 groups.", + "The ratio of TGF-beta1 absorbed light value to GAPDH absorbed light value in the SHR group was 0.887+/-0.019, which was significantly higher than that in WKY group, imidapril group, and irbesartan group with the ratios of 0.780+/-0.018, 0.803+/-0.005, and 0.847+/-0.017, respectively (P<0.01).", + "Ang II level in plasma and mesenteric arteries in imidapril group was significantly lower than that in irbesartan group (P<0.05).", + "The c-Jun absorbed light value/GAPDH absorbed light value of mesenteric arteries in the SHR group was 0.850+/-0.015, which was significantly higher than that in the WKY, imidapril, and irbesartan groups (0.582+/-0.013, 0.743+/-0.012, and 0.789+/-0.013, respectively, P<0.01), and was significantly lower in imidapril group than in irbesartan group (P<0.05).", + "CONCLUSION: Imidapril and irbesartan can not only control blood pressure but also inhibit mesenteric arteries remodeling and mRNA expression of TGF-beta1, c-Jun in SHR.", + "Imidapril is more effective than irbesartan.", + "Angiotensin II\nAngiotensin-Converting Enzyme Inhibitors\nAnimals\nAntihypertensive Agents\nBiphenyl Compounds\nBlood Pressure\nFemale\nHumans\nImidazolidines\nIrbesartan\nMale\nMesenteric Arteries\nProto-Oncogene Proteins c-jun\nRandom Allocation\nRats\nRats, Inbred SHR\nRats, Inbred WKY\nTetrazoles\nTransforming Growth Factor beta\nTransforming Growth Factor beta1" + ], + "sentences": [ + "drugbank-id: DB01029; name: Irbesartan; description: The metabolism of Estradiol can be decreased when combined with Irbesartan.; parent_key: DB00783.", + "drugbank-id: DB11783; name: Imidapril; description: Remifentanil may decrease the antihypertensive activities of Imidapril.; parent_key: DB00899.", + "drugbank-id: DB09329; name: Antihemophilic Factor (Recombinant), PEGylated; description: Cefotiam may decrease the excretion rate of Antihemophilic Factor (Recombinant), PEGylated which could result in a higher serum level.; parent_key: DB00229.", + "drugbank-id: DB11783; name: Imidapril; description: Dihydroergocornine may decrease the antihypertensive activities of Imidapril.; parent_key: DB11273.", + "drugbank-id: DB01029; name: Irbesartan; description: The metabolism of Irbesartan can be decreased when combined with Nilutamide.; parent_key: DB00665.", + "drugbank-id: DB11783; name: Imidapril; description: Sumatriptan may decrease the antihypertensive activities of Imidapril.; parent_key: DB00669.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Valbenazine which could result in a higher serum level.; parent_key: DB11915.", + "drugbank-id: DB01029; name: Irbesartan; description: The metabolism of Irbesartan can be decreased when combined with Cabergoline.; parent_key: DB00248.", + "drugbank-id: DB11783; name: Imidapril; description: Cariprazine may decrease the antihypertensive activities of Imidapril.; parent_key: DB06016.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Rosiglitazone which could result in a higher serum level.; parent_key: DB00412.", + "drugbank-id: DB01029; name: Irbesartan; description: Dopexamine may decrease the antihypertensive activities of Irbesartan.; parent_key: DB12313.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Furosemide which could result in a higher serum level.; parent_key: DB00695.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Palonosetron which could result in a higher serum level.; parent_key: DB00377.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Eucalyptus oil which could result in a higher serum level.; parent_key: DB11114.", + "drugbank-id: DB12035; name: Sarecycline; description: The risk or severity of pseudotumor cerebri and elevated intracranial pressure can be increased when Vitamin A is combined with Sarecycline.; parent_key: DB00162.", + "drugbank-id: DB11783; name: Imidapril; description: Propiomazine may decrease the antihypertensive activities of Imidapril.; parent_key: DB00777.", + "drugbank-id: DB11783; name: Imidapril; description: Methysergide may decrease the antihypertensive activities of Imidapril.; parent_key: DB00247.", + "drugbank-id: DB01029; name: Irbesartan; description: The metabolism of Irbesartan can be decreased when combined with Ketoconazole.; parent_key: DB01026.", + "drugbank-id: DB08895; name: Tofacitinib; description: Peginterferon alfa-2a may increase the immunosuppressive activities of Tofacitinib.; parent_key: DB00008.", + "drugbank-id: DB11783; name: Imidapril; description: Dimetacrine may decrease the antihypertensive activities of Imidapril.; parent_key: DB08996.", + "drugbank-id: DB00723; name: Methoxamine; description: Bromocriptine may increase the hypertensive and vasoconstricting activities of Methoxamine.; parent_key: DB01200.", + "drugbank-id: DB11783; name: Imidapril; description: Melitracen may decrease the antihypertensive activities of Imidapril.; parent_key: DB13384.", + "drugbank-id: DB11783; name: Imidapril; description: Thioridazine may decrease the antihypertensive activities of Imidapril.; parent_key: DB00679.", + "drugbank-id: DB01029; name: Irbesartan; description: The metabolism of Manidipine can be decreased when combined with Irbesartan.; parent_key: DB09238.", + "drugbank-id: DB01029; name: Irbesartan; description: Bambuterol may decrease the antihypertensive activities of Irbesartan.; parent_key: DB01408.", + "drugbank-id: DB00384; name: Triamterene; description: The metabolism of Triamterene can be increased when combined with Etanercept.; parent_key: DB00005.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Amrinone which could result in a higher serum level.; parent_key: DB01427.", + "drugbank-id: DB01029; name: Irbesartan; description: Hydracarbazine may increase the hypotensive activities of Irbesartan.; parent_key: DB09243.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Chlorzoxazone which could result in a higher serum level.; parent_key: DB00356.", + "drugbank-id: DB00036; name: Coagulation factor VIIa Recombinant Human; description: The therapeutic efficacy of Coagulation factor VIIa Recombinant Human can be decreased when used in combination with Argatroban.; parent_key: DB00278.", + "drugbank-id: DB08858; name: cis-Diamminechlorocholylglycinateplatinum(II); description: The therapeutic efficacy of cis-Diamminechlorocholylglycinateplatinum(II) can be decreased when used in combination with Ethinylestradiol.; parent_key: DB00977.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Micronomicin which could result in a higher serum level.; parent_key: DB13274.", + "drugbank-id: DB11783; name: Imidapril; description: Propiverine may decrease the antihypertensive activities of Imidapril.; parent_key: DB12278.", + "drugbank-id: DB00068; name: Interferon beta-1b; description: The metabolism of Temafloxacin can be decreased when combined with Interferon beta-1b.; parent_key: DB01405.", + "drugbank-id: DB01029; name: Irbesartan; description: The metabolism of Irbesartan can be decreased when combined with Bosutinib.; parent_key: DB06616.", + "drugbank-id: DB01381; name: Ginkgo biloba; description: The therapeutic efficacy of Abciximab can be increased when used in combination with Ginkgo biloba.; parent_key: DB00054.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Topiroxostat which could result in a higher serum level.; parent_key: DB01685.", + "drugbank-id: DB13014; name: Hypericin; description: The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Hypericin.; parent_key: DB00008.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Imipramine which could result in a higher serum level.; parent_key: DB00458.", + "drugbank-id: DB11783; name: Imidapril; description: Etafedrine may decrease the antihypertensive activities of Imidapril.; parent_key: DB11587.", + "drugbank-id: DB11783; name: Imidapril; description: Opipramol may decrease the antihypertensive activities of Imidapril.; parent_key: DB12930.", + "drugbank-id: DB03450; name: Cephalothin Group; description: The risk or severity of nephrotoxicity and hypocalcemia can be increased when Cephalothin Group is combined with Etidronic acid.; parent_key: DB01077.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Pregabalin which could result in a higher serum level.; parent_key: DB00230.", + "drugbank-id: DB01029; name: Irbesartan; description: The metabolism of Elagolix can be decreased when combined with Irbesartan.; parent_key: DB11979.", + "drugbank-id: DB11976; name: Anifrolumab; description: The risk or severity of adverse effects can be increased when Omalizumab is combined with Anifrolumab.; parent_key: DB00043.", + "drugbank-id: DB01029; name: Irbesartan; description: The metabolism of Tucatinib can be decreased when combined with Irbesartan.; parent_key: DB11652.", + "drugbank-id: DB01029; name: Irbesartan; description: Vilanterol may decrease the antihypertensive activities of Irbesartan.; parent_key: DB09082.", + "drugbank-id: DB11783; name: Imidapril; description: Phenmetrazine may decrease the antihypertensive activities of Imidapril.; parent_key: DB00830.", + "drugbank-id: DB03450; name: Cephalothin Group; description: Cephalothin Group may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level.; parent_key: DB09066.", + "drugbank-id: DB11783; name: Imidapril; description: Trazodone may decrease the antihypertensive activities of Imidapril.; parent_key: DB00656." + ] + }, + { + "example_idx": 50, + "anchor_id": 7975653793909382669, + "positive_id": 15341181862965757810, + "join_paths": [ + [ + 13, + 43, + 0.291015625 + ], + [ + 19, + 25, + 0.21875 + ], + [ + 19, + 43, + 0.1875 + ], + [ + 17, + 28, + 0.1552734375 + ], + [ + 19, + 21, + 0.1552734375 + ] + ], + "rows": [ + "PURPOSE: Expression of the Bcl-2 protein confers resistance to various apoptotic signals.", + "G3139 [oblimersen sodium (Genasense)] is a phosphorothioate antisense oligodeoxynucleotide that targets Bcl-2 mRNA, downregulates Bcl-2 protein translation, and enhances the antitumor effects of subtherapeutic doses of docetaxel (Taxotere).", + "PATIENTS AND METHODS: We performed a phase I trial to determine the maximum tolerated dose (MTD) and safety profile of combined therapy with G3139 and weekly docetaxel in patients with advanced Bcl-2-positive solid tumors.", + "Cohorts of three to six patients were enrolled to escalating doses of G3139 and a fixed dose of weekly docetaxel using either of two schedules.", + "In part I, G3139 was administered by continuous infusion for 21 days (D1-22), and docetaxel (35 mg/m2) was given weekly on days 8, 15 and 22.", + "In part II, G3139 was given by continuous infusion for 5 days before the first weekly dose of docetaxel, and for 48 h before the second and third weekly docetaxel doses.", + "For both schedules, cycles were repeated every 4 weeks.", + "RESULTS: Twenty-two patients were enrolled.", + "Thirteen patients were treated on the part I schedule with doses of G3139 escalated from 1 to 4 mg/kg/day.", + "Nine patients were on the part II schedule of shorter G3139 infusion at G3139 doses of 5-9 mg/kg/day.", + "Hematologic toxicities were mild, except for one case of persistent grade 3 thrombocytopenia in part I.", + "The most common adverse events were cumulative fatigue and transaminase elevation, which prevented further dose escalation beyond 4 mg/kg/day for 21 days with the part I schedule.", + "In part II of the study, using the abbreviated G3139 schedule, even the highest daily doses were tolerated without dose-limiting toxicity or the need for dose modification.", + "Objective tumor response was observed in two patients with breast cancer, including one whose cancer previously progressed on trastuzumab plus paclitaxel.", + "Four patients had stable disease.", + "Pharmacokinetic results for G3139 were similar to those of other trials.", + "CONCLUSIONS: G3139 in combination with standard-dose weekly docetaxel was well tolerated.", + "The shortened and intermittent G3139 infusion had less cumulative toxicities and still allowed similar total G3139 delivery as the longer infusion.", + "Further studies should examine the molecular effect of the regimen, as well as clinical activities in malignancies for which taxanes are indicated.", + "Adult\nAged\nAntineoplastic Agents, Phytogenic\nBreast Neoplasms\nDocetaxel\nDrug Administration Schedule\nFemale\nHumans\nInfusions, Intravenous\nMaximum Tolerated Dose\nMiddle Aged\nNeoplasms\nTaxoids\nThionucleotides\nTreatment Outcome" + ], + "sentences": [ + "ref-id: L376; title: Drug Information; url: https://www.drugs.com/history/trulance.html; parent_key: DB13170.", + "ref-id: L6919; title: FDA Approved Drug Products: Eculizumab Intravenous Infusion; url: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125166; parent_key: DB01257.", + "ref-id: L1931; title: National Cancer Institute; url: https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq; parent_key: DB09053.", + "ref-id: L2348; title: Burosumab for a rare bone disease; url: http://www.who.int/medicines/publications/druginformation/issues/WHO_DI_32-1.pdf; parent_key: DB14012.", + "ref-id: L2069; title: Heart and stroke foundation; url: http://www.heartandstroke.ca/stroke/what-is-stroke; parent_key: DB11164.", + "ref-id: L3450; title: FDA Approved Drug Products: Invirase (saquinavir mesylate) oral tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021785s024lbl.pdf; parent_key: DB01232.", + "ref-id: L1136; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/results/NCT02411929?sect=Xgf0156#outcome10; parent_key: DB11827.", + "ref-id: L13841; title: Deciphera phase 1 study results; url: https://www.deciphera.com/wp-content/uploads/2018/10/ESMO-2018-George-et-al.-for-submission-to-ESMO-final.pdf; parent_key: DB14840.", + "ref-id: L1168; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/record/NCT02612298?view=results; parent_key: DB09204.", + "ref-id: L2608; title: Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach; url: http://www.jle.com/download/mrh-267774-study_of_magnesium_bioavailability_from_ten_organic_and_inorganic_mg_salts_in_mg_depleted_rats_using_a_stable_isotope_approach--WuiPHn8AAQEAADOFX1sAAAAH-a.pdf; parent_key: DB13749.", + "ref-id: L3626; title: FDA approves first smallpox indicated treatment; url: https://www.genengnews.com/gen-news-highlights/fda-approves-first-smallpox-indicated-treatment-sigas-tpoxx/81256026; parent_key: DB12020.", + "ref-id: L2124; title: Gelatin, Lab Grade; url: https://beta-static.fishersci.com/content/dam/fishersci/en_US/documents/programs/education/regulatory-documents/sds/chemicals/chemicals-g/S25335.pdf; parent_key: DB11242.", + "ref-id: L5314; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT03172208; parent_key: DB06081.", + "ref-id: L4274; title: Amicus Therapeutics News Release: FDA Approves Galafold™ (migalastat) for the Treatment of Certain Adult Patients with Fabry Disease; url: http://ir.amicusrx.com/news-releases/news-release-details/fda-approves-galafoldtm-migalastat-treatment-certain-adult; parent_key: DB05018.", + "ref-id: L1316; title: Melperone (an Anti-Psychotic) in Patients With Psychosis Associated With Parkinson's Disease; url: https://clinicaltrials.gov/ct2/show/NCT00125138; parent_key: DB09224.", + "ref-id: L2336; title: Opicapone:once-daily adjunctive therapy for Parkinson’s disease; url: https://onlinelibrary.wiley.com/doi/pdf/10.1002/psb.1543; parent_key: DB11632.", + "ref-id: L5876; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02499146; parent_key: DB09073.", + "ref-id: L4841; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01818492; parent_key: DB14724.", + "ref-id: L4835; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02456883; parent_key: DB12141.", + "ref-id: L5798; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01123486; parent_key: DB00327.", + "ref-id: L2604; title: Mg products; url: http://www.globalrph.com/magnesium_supplements.htm; parent_key: DB13749.", + "ref-id: L2165; title: Antiperspirants/Deodorants and Breast Cancer; url: https://www.cancer.gov/about-cancer/causes-prevention/risk/myths/antiperspirants-fact-sheet; parent_key: DB11239.", + "ref-id: L1233; title: Comparison of Pharmacokinetics between Loxoprofen and Its Derivative with Lower Ulcerogenic Activity, Fluoro-loxoprofen; url: https://pdfs.semanticscholar.org/6f52/9ebb1b417438f2ca462c82d4720b30606a48.pdf; parent_key: DB09212.", + "ref-id: L2018; title: Clinical pharmacology of atypical antipsychotics: an update; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464358/; parent_key: DB00502.", + "ref-id: L2709; title: Breast Cancer Organization, UK; url: https://www.breastcanceruk.org.uk/science-and-research/background-briefings/aluminium-salts/; parent_key: DB11200.", + "ref-id: L2168; title: BREAST CANCER AND DEODORANTS/ ANTIPERSPIRANTS: A SYSTEMATIC REVIEW; url: https://pdfs.semanticscholar.org/2877/4ce8ef9459eac3d0fb8ef8db755aa75dc492.pdf; parent_key: DB11239.", + "ref-id: L4588; title: Cancer.gov; url: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma; parent_key: DB11952.", + "ref-id: L2167; title: Underarm antiperspirants/deodorants and breast cancer; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797685/; parent_key: DB11239.", + "ref-id: L1678; title: Toxicokinetics of Mercury after Long-Term Repeated Exposure to Thimerosal-Containing Vaccine; url: https://watermark.silverchair.com/kfr009.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAakwggGlBgkqhkiG9w0BBwagggGWMIIBkgIBADCCAYsGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMW0bWnQIT2cgCI9grAgEQgIIBXConbxAIybSm8nt9sq3XLD6FXwk5iR6JvWmt0TZ_eNo1i23x9WAeA27ZgFUJjbtsNrf_SPnPqljOSDTHviFNpDedT1VXht8CrynwJnGIxKgYSgTlvvLMTp529pd4W1rfpurel-Dtb0SEV2z7S5DC8sgbttUwVZldRaQX-BnhUB80qyNopJumFasQtCI2fv1mVs8_jcnECqFbIHY-QMKCcsSB9VYf1hNwnF0sNqPWBVjl-bP8Za1Wjq01NGA9qQUhdZ92c5jGmyFRBhZdbxmOC-9VzwcefYnWxb3C-5DbmOgg7dy3E9o-7JKuOqJWR4Earir-bepLCUqER5TQwzJ-P3XMEWqkuZeVDC7E5mfneV-uVSk7pFVKxLYfkDxma_e-s0xwm2G0DKCPUG2gAMaOcxTaRM2ybi3dOf-X_Hks3ZhQbocEy3ngvPbkmNmnDGzHK67asKvJr9LN27wFdQ; parent_key: DB11590.", + "ref-id: L2965; title: Enhancement of Tumor Response to -Radiation by an Inhibitor of Cyclooxygenase-2 Enzyme; url: https://www.researchgate.net/publication/31132809_Enhancement_of_Tumor_Response_to_-Radiation_by_an_Inhibitor_of_Cyclooxygenase-2_Enzyme; parent_key: DB14059.", + "ref-id: L2339; title: Clinical pharmacology review of opicapone for the treatment of Parkinson's disease; url: https://www.futuremedicine.com/doi/10.2217/nmt-2016-0022; parent_key: DB11632.", + "ref-id: L5200; title: Xeris Pharmaceuticals Awarded Phase I-II NIH SBIR Fast Track Grant to Advance a Stable, Non-Aqueous Diazepam, Subcutaneous Injection for Treatment of Acute Repetitive Seizures in Patients with Epilepsy: Press Release; url: https://globenewswire.com/news-release/2015/10/01/772768/0/en/Xeris-Pharmaceuticals-Awarded-Phase-I-II-NIH-SBIR-Fast-Track-Grant-to-Advance-a-Stable-Non-Aqueous-Diazepam-Subcutaneous-Injection-for-Treatment-of-Acute-Repetitive-Seizures-in-Pat.html; parent_key: DB00829.", + "ref-id: L1651; title: Cancer; url: https://www.cancer.org/cancer/small-cell-lung-cancer/about/what-is-small-cell-lung-cancer.html; parent_key: DB09336.", + "ref-id: L6601; title: FDA Approved Drug Products: Actiq Transmucosal Lozenge; url: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020747; parent_key: DB00813.", + "ref-id: L2323; title: Pharmacokinetic Studies on Propiverine Hydrochloride; url: https://www.jstage.jst.go.jp/article/dmpk1986/10/2/10_2_205/_article; parent_key: DB12278.", + "ref-id: L11031; title: FDA Approved Drug Products: Zyrtec Cetirizine and Pseudoephedrine Oral Tablets (OTC); url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19835slr016,21150slr005,30346slr011_zyrtec_lbl.pdf; parent_key: DB00852.", + "ref-id: L2055; title: Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency; url: https://onlinelibrary.wiley.com/doi/pdf/10.1002/mnfr.201500019; parent_key: DB11191.", + "ref-id: L11860; title: Federal Register: Withdrawal of Approval of 29 NADA's (July 3, 1996); url: https://www.govinfo.gov/content/pkg/FR-1996-07-03/html/96-16887.htm; parent_key: DB06803.", + "ref-id: L13859; title: Deciphera phase 3 study results; url: https://www.deciphera.com/wp-content/uploads/2019/11/CTOS-2019-INVICTUS-Oral-Presentation-FINAL_Nov-15.pdf; parent_key: DB14840.", + "ref-id: L12843; title: Clinical Trials: COVACTA; url: https://clinicaltrials.gov/ct2/show/NCT04320615; parent_key: DB06273.", + "ref-id: L356; title: Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771396/; parent_key: DB11737.", + "ref-id: L5933; title: Diabetes, Heart Disease, and Stroke: NIDDK; url: https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/heart-disease-stroke; parent_key: DB08907.", + "ref-id: L4799; title: Sandoz received US FDA approval for bio similar, Hyrimoz; url: https://www.novartis.com/news/media-releases/sandoz-receives-us-fda-approval-biosimilar-hyrimoztm-adalimumab-adaz; parent_key: DB00051.", + "ref-id: L10845; title: FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies; url: https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-option-patients-her2-positive-breast-cancer-who-have-progressed-available; parent_key: DB14962.", + "ref-id: L2560; title: Examine; url: https://examine.com/supplements/inositol/; parent_key: DB13178.", + "ref-id: L1317; title: The effect of melperone, an atypical antipsychotic drug, on cognitive function in schizophrenia; url: https://www.sciencedirect.com/science/article/pii/S0920996401003292; parent_key: DB09224.", + "ref-id: L4834; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02181660; parent_key: DB12141.", + "ref-id: L7126; title: Clinical Trials: BOSTON Trial; url: https://clinicaltrials.gov/ct2/show/NCT03110562; parent_key: DB11942.", + "ref-id: L2932; title: Avatrombopag Gains FDA Approval for Patients with Chronic Liver Disease; url: https://www.specialtypharmacytimes.com/news/avatrombopag-gains-fda-approval-for-patients-with-chronic-liver-disease; parent_key: DB11995.", + "ref-id: L1823; title: Wilson Disease; url: https://www.niddk.nih.gov/health-information/liver-disease/wilson-disease; parent_key: DB06778." + ] + }, + { + "example_idx": 51, + "anchor_id": 9479311653239215871, + "positive_id": 13125769954515235916, + "join_paths": [ + [ + 9, + 1, + 0.2333984375 + ], + [ + 9, + 16, + 0.2333984375 + ], + [ + 9, + 19, + 0.2333984375 + ], + [ + 0, + 16, + 0.2314453125 + ], + [ + 9, + 8, + 0.2314453125 + ] + ], + "rows": [ + "Histamine H1-receptor (H1R) antagonists, or antihistamines, often induce sedative side effects when used for the treatment of allergic disorders.", + "This study compared the sedative profiles of the second-generation antihistamines, fexofenadine and cetirizine, using 3 different criteria: subjective sleepiness evaluated by the Stanford Sleepiness Scale, objective psychomotor tests (simple and choice reaction time tests and visual discrimination tests at 4 different exposure durations), and measurement of histamine H1-receptor occupancy (H1RO) in the brain.", + "Subjective sleepiness and psychomotor performance were measured in 20 healthy Japanese volunteers at baseline and 90 min after administration of fexofenadine 120 mg or cetirizine 20 mg in a double-blind, placebo-controlled crossover study.", + "Hydroxyzine 30 mg was included as a positive control.", + "H1RO was measured using positron emission tomography (PET) with (11)C-doxepin in 12 of the 20 subjects, and a further 11 volunteers were recruited to act as controls.", + "In psychomotor tests, fexofenadine was not significantly different from placebo and significantly less impairing than cetirizine on some tasks, as well as significantly less impairing than hydroxyzine on all tasks.", + "For subjective sleepiness, fexofenadine was not significantly different from placebo, whereas cetirizine showed a trend toward increased sleepiness compared with fexofenadine and placebo.", + "H1RO was negligible with fexofenadine (-0.1%) but moderately high with cetirizine (26.0%).", + "In conclusion, fexofenadine 120 mg is distinguishable from cetirizine 20 mg, as assessed by H1RO and psychomotor testing.", + "Adult\nBrain\nCarbon Radioisotopes\nCetirizine\nCross-Over Studies\nDouble-Blind Method\nDoxepin\nHistamine H1 Antagonists\nHistamine H1 Antagonists, Non-Sedating\nHumans\nMale\nPositron-Emission Tomography\nPractice Guidelines as Topic\nPsychomotor Performance\nReceptors, Histamine H1\nSleep Stages\nTerfenadine" + ], + "sentences": [ + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 13; parent_key: DB00555.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 4; parent_key: DB01151.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 5; parent_key: DB01239.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB01624.", + "id: BE0000945; name: 5-hydroxytryptamine receptor 6; organism: Humans; known_action: unknown; position: 4; parent_key: DB09225.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00434.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB08799.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00283.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB01267.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00366.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00835.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01071.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00985.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 11; parent_key: DB01238.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 2; parent_key: DB00934.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB11235.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB09167.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; parent_key: DB05492.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01142.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB01175.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 16; parent_key: DB00543.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 10; parent_key: DB04946.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB09555.", + "id: BE0000499; name: Low-density lipoprotein receptor; organism: Humans; known_action: unknown; parent_key: DB00707.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01620.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB06678.", + "id: BE0000829; name: Glutamate receptor 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB08305.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 4; parent_key: DB07724.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01146.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00405.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB04841.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00972.", + "id: BE0000836; name: Hydroxycarboxylic acid receptor 3; organism: Humans; known_action: yes; position: 3; parent_key: DB08949.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01237.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 12; parent_key: DB00321.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB01615.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00792.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; parent_key: DB00370.", + "id: BE0001898; name: Heat shock protein HSP 90-beta; organism: Humans; known_action: unknown; position: 1; parent_key: DB08153.", + "id: BE0004888; name: Alpha adrenergic receptor; organism: Humans; known_action: unknown; position: 8; parent_key: DB01069.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB00629.", + "id: BE0000405; name: Muscarinic acetylcholine receptor M4; organism: Humans; known_action: no; position: 22; parent_key: DB00363.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB00246.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: no; position: 17; parent_key: DB14185.", + "id: BE0009927; name: Neuronal Acetylcholine (nACh) Receptor Subunits; organism: Humans; known_action: unknown; position: 2; parent_key: DB00237.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB08801.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB06148.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00427.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; parent_key: DB00950.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB00715." + ] + }, + { + "example_idx": 52, + "anchor_id": 13360989878832871933, + "positive_id": 13385371400272512400, + "join_paths": [ + [ + 0, + 6, + 0.1923828125 + ], + [ + 0, + 11, + 0.1923828125 + ], + [ + 0, + 3, + 0.19140625 + ], + [ + 0, + 42, + 0.19140625 + ], + [ + 0, + 10, + 0.1904296875 + ] + ], + "rows": [ + "Clinical studies have indicated that a low dose of the dopamine D2-receptor antagonist droperidol given epidurally potentiate the antinociceptive effect of epidural morphine.", + "The present study was conducted in order to evaluate this drug interaction in a rat model.", + "Rats were given morphine and droperidol intrathecally in several combinations of doses.", + "It was found that droperidol had no antinociceptive effect by itself, nor in combination with morphine.", + "It was also shown that droperidol and morphine exert no histopathological effects on the rat spinal cord.", + "This discrepancy between clinical findings and experimental pain studies suggests different modes of action of droperidol in the two situations.", + "Animals\nDose-Response Relationship, Drug\nDroperidol\nDrug Synergism\nInjections, Spinal\nMale\nMorphine\nRats\nRats, Inbred Strains\nSpinal Cord" + ], + "sentences": [ + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00409.", + "id: BE0003721; name: Aryl hydrocarbon receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB11577.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: unknown; position: 1; parent_key: DB07032.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB00543.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB09018.", + "id: BE0003721; name: Aryl hydrocarbon receptor; organism: Humans; known_action: unknown; position: 10; parent_key: DB00393.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB01221.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01403.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; parent_key: DB06288.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; parent_key: DB01233.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 13; parent_key: DB00934.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB09207.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB00777.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB09224.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 10; parent_key: DB00182.", + "id: BE0000841; name: Ephrin type-A receptor 2; organism: Humans; known_action: yes; position: 3; parent_key: DB01254.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB01235.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00831.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00714.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB09194.", + "id: BE0000945; name: 5-hydroxytryptamine receptor 6; organism: Humans; known_action: unknown; position: 15; parent_key: DB01238.", + "id: BE0000033; name: Insulin receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00071.", + "id: BE0000289; name: Alpha-2A adrenergic receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB00320.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB11274.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB01623.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; parent_key: DB05964.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00875.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; parent_key: DB05766.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; parent_key: DB00490.", + "id: BE0002442; name: Toll-like receptor 4; organism: Humans; known_action: unknown; position: 3; parent_key: DB02767.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00420.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01100.", + "id: BE0000346; name: Glutamate receptor ionotropic, kainate 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00237.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB08815.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; parent_key: DB04857.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB01238.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB09223.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01038.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00363.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB00540.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; parent_key: DB12061.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; parent_key: DB06477.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 18; parent_key: DB01151.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01425.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; parent_key: DB06077.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01622.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB01392.", + "id: BE0000623; name: Tyrosine-protein phosphatase non-receptor type 1; organism: Humans; known_action: unknown; parent_key: DB05506.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 9; parent_key: DB01175.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00988." + ] + }, + { + "example_idx": 53, + "anchor_id": 4453301489573101284, + "positive_id": 7948004871518673350, + "join_paths": [ + [ + 6, + 14, + 0.318359375 + ], + [ + 6, + 44, + 0.31640625 + ], + [ + 6, + 10, + 0.3125 + ], + [ + 6, + 24, + 0.3125 + ], + [ + 6, + 25, + 0.310546875 + ] + ], + "rows": [ + "The N-methyl-d-aspartate (NMDA) receptor antagonist memantine is an approved drug for treatment of Alzheimer's disease (AD).", + "Other such treatments are cholinesterase inhibitors and nicotinic acetylcholine receptor (nAChR)-sensitizing agents such as galantamine.", + "The present study was designed to test whether memantine exerts any effect on the cholinergic system, in particular the Ca(2+)-conducting alpha7(*) nAChR, in cultured hippocampal neurons.", + "Memantine caused a concentration-dependent reduction of the amplitudes of whole-cell currents evoked by the alpha7(*) nAChR-selective agonist choline (10 mM) or by N-methyl-d-aspartate (NMDA) (50 muM) plus glycine (10 muM).", + "It also inhibited tonically activated NMDA receptors.", + "Memantine was more potent in inhibiting alpha7(*) nAChRs than NMDA receptors; at -60 mV, the IC(50) values for memantine were 0.34 and 5.1 muM, respectively.", + "Consistent with an open-channel blocking mechanism, memantine-induced NMDA receptor inhibition was voltage and use-dependent; the Hill coefficient (n(H)) was approximately 1.", + "Memantine-induced alpha7(*) nAChR inhibition had an n(H) < 1 and showed a variable voltage dependence; the effect was voltage-independent at 0.1 muM, becoming voltage-dependent at >/=1 muM.", + "Thus, memantine interacts with more than one class of sites on the alpha7(*) nAChRs.", + "One is voltage-sensitive and therefore likely to be within the receptor channel.", + "The other is voltage-insensitive and therefore likely to be in the extracellular domain of the receptor.", + "It is suggested that blockade of alpha7(*) nAChRs by memantine could decrease its effectiveness for treatment of AD, particularly at early stages when the degrees of nAChR dysfunction and of cognitive decline correlate well.", + "Animals\nDose-Response Relationship, Drug\nExcitatory Amino Acid Antagonists\nHippocampus\nMemantine\nMembrane Potentials\nNicotinic Antagonists\nRats\nRats, Sprague-Dawley\nReceptors, N-Methyl-D-Aspartate\nReceptors, Nicotinic\nalpha7 Nicotinic Acetylcholine Receptor" + ], + "sentences": [ + "id: BE0009666; name: Glycine receptors; organism: Humans; known_action: unknown; position: 13; parent_key: DB01043.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB11273.", + "id: BE0000644; name: ATP-sensitive inward rectifier potassium channel 1; organism: Humans; known_action: yes; parent_key: DB01382.", + "id: BE0000829; name: Glutamate receptor 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB01352.", + "id: BE0008715; name: Voltage-dependent L-type calcium channel; organism: Humans; known_action: yes; position: 1; parent_key: DB00653.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; position: 1; parent_key: DB08201.", + "id: BE0000495; name: Amiloride-sensitive sodium channel subunit delta; organism: Humans; known_action: unknown; parent_key: DB00384.", + "id: BE0003438; name: Alpha-7 nicotinic cholinergic receptor subunit; organism: Humans; known_action: unknown; position: 7; parent_key: DB00193.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09194.", + "id: BE0000644; name: ATP-sensitive inward rectifier potassium channel 1; organism: Humans; known_action: yes; parent_key: DB00350.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 18; parent_key: DB01174.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 13; parent_key: DB00477.", + "id: BE0003635; name: Sodium channel subunit beta-1; organism: Humans; known_action: yes; position: 8; parent_key: DB00909.", + "id: BE0004905; name: ATP-sensitive potassium channel; organism: Humans; known_action: yes; position: 5; parent_key: DB11148.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB11823.", + "id: BE0000850; name: Neuronal acetylcholine receptor subunit beta-2; organism: Humans; known_action: unknown; parent_key: DB05458.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 7; parent_key: DB01186.", + "id: BE0004902; name: Voltage-dependent calcium channel; organism: Humans; known_action: unknown; position: 3; parent_key: DB13746.", + "id: BE0008717; name: Voltage-dependent P/Q-type calcium channel; organism: Humans; known_action: unknown; position: 5; parent_key: DB13746.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 11; parent_key: DB01239.", + "id: BE0008716; name: Voltage-dependent T-type calcium channel; organism: Humans; known_action: unknown; position: 4; parent_key: DB09089.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 2; parent_key: DB00677.", + "id: BE0000959; name: Fatty acid synthase; organism: Humans; known_action: yes; position: 4; parent_key: DB01034.", + "id: BE0000710; name: High affinity immunoglobulin gamma Fc receptor I; organism: Humans; known_action: unknown; parent_key: DB00056.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 14; parent_key: DB00312.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00874.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 1; parent_key: DB00545.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; parent_key: DB00217.", + "id: BE0002084; name: Sodium channel protein type 8 subunit alpha; organism: Humans; known_action: yes; position: 19; parent_key: DB00252.", + "id: BE0008716; name: Voltage-dependent T-type calcium channel; organism: Humans; known_action: yes; position: 3; parent_key: DB09231.", + "id: BE0002441; name: ATP-sensitive inward rectifier potassium channel 8; organism: Humans; known_action: yes; parent_key: DB00922.", + "id: BE0000687; name: Thyroid hormone receptor alpha; organism: Humans; known_action: yes; parent_key: DB00451.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB04250.", + "id: BE0001019; name: Mitogen-activated protein kinase 14; organism: Humans; known_action: unknown; position: 1; parent_key: DB08242.", + "id: BE0000644; name: ATP-sensitive inward rectifier potassium channel 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB01124.", + "id: BE0000509; name: Extracellular calcium-sensing receptor; organism: Humans; known_action: unknown; parent_key: DB05255.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09304.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 2; parent_key: DB00841.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: yes; position: 5; parent_key: DB00368.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 17; parent_key: DB00543.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; position: 1; parent_key: DB08658.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB01049.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; parent_key: DB00697.", + "id: BE0004923; name: Mitochondrial ATP-sensitive potassium channel; organism: Humans; known_action: unknown; position: 8; parent_key: DB01016.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB01708.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB03814.", + "id: BE0004902; name: Voltage-dependent calcium channel; organism: Humans; known_action: yes; position: 1; parent_key: DB11148.", + "id: BE0000029; name: Vascular endothelial growth factor receptor 1; organism: Humans; known_action: yes; position: 2; parent_key: DB10770.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; parent_key: DB00941.", + "id: BE0000509; name: Extracellular calcium-sensing receptor; organism: Humans; known_action: unknown; parent_key: DB05695." + ] + }, + { + "example_idx": 54, + "anchor_id": 7303988896391934198, + "positive_id": 13993808475230968697, + "join_paths": [ + [ + 7, + 30, + 0.255859375 + ], + [ + 1, + 30, + 0.248046875 + ], + [ + 4, + 30, + 0.248046875 + ], + [ + 0, + 2, + 0.24609375 + ], + [ + 1, + 2, + 0.24609375 + ] + ], + "rows": [ + "Irinotecan hydrochloride (CPT-11) is a potent anticancer drug that is converted to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), and other metabolites in liver.", + "The disposition and gastrointestinal toxicity of irinotecan exhibit a wide interpatient variability.", + "Here, we examined the contribution of an organic anion-transporting polypeptide, OATP1B1 (OATP-C), which transports a variety of drugs and their metabolites from blood to liver in humans, to the hepatic disposition of irinotecan, SN-38, and its glucuronide conjugate (SN-38G) by using HEK293 cells stably transfected with SLCO1B1*1a (OATP-C*1a) coding wild-type OATP1B1.", + "We further examined the effect of single nucleotide polymorphisms in OATP1B1 by measuring uptake activity in Xenopus oocytes expressing OATP1B1*1a and three common variants.", + "In all cases, transport activity for SN-38 was observed, whereas irinotecan and SN-38G were not transported.", + "Moreover, SN-38 exhibited a significant inhibitory effect on OATP1B1-mediated uptake of [(3)H]estrone-3-sulfate.", + "Among the variants examined, OATP1B1*15 (N130D and V174A; reported allele frequency 10-15%) exhibited decreased transport activities for SN-38 as well as pravastatin, estrone-3-sulfate, and estradiol-17beta-glucuronide.", + "This study is the first to yield evidence that OATP1B1 is involved in the hepatic disposition of SN-38 and that genetic polymorphisms of OATP1B1 may contribute to the known interpatient variability in disposition of irinotecan.", + "Animals\nAntineoplastic Agents, Phytogenic\nCamptothecin\nCell Line\nCells, Cultured\nEstrone\nFemale\nGlucuronides\nHumans\nIrinotecan\nLiver\nLiver-Specific Organic Anion Transporter 1\nOocytes\nPolymorphism, Single Nucleotide\nTopoisomerase I Inhibitors\nXenopus" + ], + "sentences": [ + "sequence: 1; left_drugbank_id: DB00864; left_drugbank_name: Tacrolimus; right_drugbank_id: DBMET01668; right_drugbank_name: 15-O-Desmethyltacrolimus; parent_key: DB00864.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET00530; right_drugbank_name: Estrone sulfate; parent_key: DB00655.", + "sequence: 1; left_drugbank_id: DB00762; left_drugbank_name: Irinotecan; right_drugbank_id: DBMET01681; right_drugbank_name: 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin; parent_key: DB00762.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET01666; right_drugbank_name: 16beta-OH-estrone; parent_key: DB00655.", + "sequence: 2; left_drugbank_id: DBMET00490; left_drugbank_name: Estrone; right_drugbank_id: DBMET00530; right_drugbank_name: Estrone sulfate; parent_key: DB00783.", + "sequence: 1; left_drugbank_id: DB00481; left_drugbank_name: Raloxifene; right_drugbank_id: DBMET02524; right_drugbank_name: Raloxifene-4′-glucuronide; parent_key: DB00481.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET01665; right_drugbank_name: 16alpha-OH-estrone; parent_key: DB00655.", + "sequence: 1; left_drugbank_id: DB00175; left_drugbank_name: Pravastatin; right_drugbank_id: DBMET02472; right_drugbank_name: 6-epi-pravastatin; parent_key: DB00175.", + "sequence: 2; left_drugbank_id: DBMET01020; left_drugbank_name: (R)-MHD; right_drugbank_id: DBMET02803; right_drugbank_name: trans-10,11-dihydro-10,11-dihydroxycarbamazepine; parent_key: DB00776.", + "sequence: 1; left_drugbank_id: DB00175; left_drugbank_name: Pravastatin; right_drugbank_id: DBMET02473; right_drugbank_name: Triol pravastatin; parent_key: DB00175.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET01661; right_drugbank_name: 6alpha-OH-estrone; parent_key: DB00655.", + "sequence: 2; left_drugbank_id: DBMET01143; left_drugbank_name: SN-38; right_drugbank_id: DBMET03116; right_drugbank_name: 10-O-glucuronyl-SN-38; parent_key: DB12893.", + "sequence: 1; left_drugbank_id: DB00783; left_drugbank_name: Estradiol; right_drugbank_id: DBMET00567; right_drugbank_name: Estradiol-17beta 3-sulfate; parent_key: DB00783.", + "sequence: 3; left_drugbank_id: DBMET01063; left_drugbank_name: Bortezomib metabolite M3; right_drugbank_id: DBMET01064; right_drugbank_name: Bortezomib metabolite M4; parent_key: DB00188.", + "sequence: 2; left_drugbank_id: DBMET00291; left_drugbank_name: 10,11-Epoxycarbamazepine; right_drugbank_id: DBMET00806; right_drugbank_name: 10,11-Dihydroxycarbamazepine; parent_key: DB00564.", + "sequence: 1; left_drugbank_id: DB00175; left_drugbank_name: Pravastatin; right_drugbank_id: DBMET02475; right_drugbank_name: pravastatin glucuronide; parent_key: DB00175.", + "sequence: 3; left_drugbank_id: DBMET02788; left_drugbank_name: desloratadine glucuronide; right_drugbank_id: DBMET02787; right_drugbank_name: 3-hydroxydesloratadine; parent_key: DB00455.", + "sequence: 2; left_drugbank_id: DBMET02861; left_drugbank_name: 20β-dihydro-prednisone (M-IV); right_drugbank_id: DBMET02862; right_drugbank_name: 17α,20ξ,21-trihydroxy-5ξ-pregn-1-en-3,11-dione(M-XVIII); parent_key: DB00635.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET01663; right_drugbank_name: 7alpha-OH-estrone; parent_key: DB00655.", + "sequence: 1; left_drugbank_id: DB00304; left_drugbank_name: Desogestrel; right_drugbank_id: DBMET01371; right_drugbank_name: 15-alpha-hydroxydesogestrel; parent_key: DB00304.", + "sequence: 2; left_drugbank_id: DBMET02759; left_drugbank_name: Methimazole Epoxide Metabolite; right_drugbank_id: DBMET02760; right_drugbank_name: Methimazole Dihydrodiol Metabolite; parent_key: DB00763.", + "sequence: 1; left_drugbank_id: DB00580; left_drugbank_name: Valdecoxib; right_drugbank_id: DBMET01344; right_drugbank_name: Valdecoxib metabolite M1; parent_key: DB00580.", + "sequence: 1; left_drugbank_id: DB04574; left_drugbank_name: Estrone sulfate; right_drugbank_id: DBMET00492; right_drugbank_name: Estriol; parent_key: DB04574.", + "sequence: 1; left_drugbank_id: DB02901; left_drugbank_name: Stanolone; right_drugbank_id: DBMET00593; right_drugbank_name: 3-alpha-Androstanediol glucuronide; parent_key: DB02901.", + "sequence: 1; left_drugbank_id: DB00783; left_drugbank_name: Estradiol; right_drugbank_id: DBMET00490; right_drugbank_name: Estrone; parent_key: DB00783.", + "sequence: 1; left_drugbank_id: DB00783; left_drugbank_name: Estradiol; right_drugbank_id: DBMET00576; right_drugbank_name: 2-methoxy-17beta-estradiol 3-O-(beta-D-glucuronide); parent_key: DB00783.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET01664; right_drugbank_name: 15alpha-OH-estrone; parent_key: DB00655.", + "sequence: 2; left_drugbank_id: DBMET02802; left_drugbank_name: (S)-MHD; right_drugbank_id: DBMET02804; right_drugbank_name: cis-10,11-dihydro-10,11-dihydroxycarbamazepine; parent_key: DB00776.", + "sequence: 1; left_drugbank_id: DB12893; left_drugbank_name: Sacituzumab govitecan; right_drugbank_id: DBMET01143; right_drugbank_name: SN-38; parent_key: DB12893.", + "sequence: 1; left_drugbank_id: DB04557; left_drugbank_name: Arachidonic Acid; right_drugbank_id: DBMET01606; right_drugbank_name: 15-HETE; parent_key: DB04557.", + "sequence: 1; left_drugbank_id: DB00762; left_drugbank_name: Irinotecan; right_drugbank_id: DBMET01143; right_drugbank_name: SN-38; parent_key: DB00762.", + "sequence: 3; left_drugbank_id: DBMET00490; left_drugbank_name: Estrone; right_drugbank_id: DBMET00491; right_drugbank_name: Estradiol; parent_key: DB00624.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET00615; right_drugbank_name: 2-Hydroxyestrone sulfate; parent_key: DB00655.", + "sequence: 2; left_drugbank_id: DBMET02802; left_drugbank_name: (S)-MHD; right_drugbank_id: DBMET02803; right_drugbank_name: trans-10,11-dihydro-10,11-dihydroxycarbamazepine; parent_key: DB00776.", + "sequence: 1; left_drugbank_id: DB04557; left_drugbank_name: Arachidonic Acid; right_drugbank_id: DBMET01602; right_drugbank_name: 14,15-EET; parent_key: DB04557.", + "sequence: 3; left_drugbank_id: DBMET02916; left_drugbank_name: α-Hydroxy sertraline ketone; right_drugbank_id: DBMET02918; right_drugbank_name: Sertraline carbamoyl-O-glucuronide; parent_key: DB01104.", + "sequence: 1; left_drugbank_id: DB00175; left_drugbank_name: Pravastatin; right_drugbank_id: DBMET02476; right_drugbank_name: 3'(S)-hydroxy-pravastatin-tetranor; parent_key: DB00175.", + "sequence: 3; left_drugbank_id: DB00154; left_drugbank_name: Dihomo-gamma-linolenic acid; right_drugbank_id: DBMET02087; right_drugbank_name: 15-HETrE; parent_key: DB11358.", + "sequence: 1; left_drugbank_id: DB00175; left_drugbank_name: Pravastatin; right_drugbank_id: DBMET02478; right_drugbank_name: 3'(S)-hydroxy-pravastatin; parent_key: DB00175.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET01660; right_drugbank_name: 4-OH-estrone; parent_key: DB00655.", + "sequence: 2; left_drugbank_id: DBMET01371; left_drugbank_name: 15-alpha-hydroxydesogestrel; right_drugbank_id: DBMET00488; right_drugbank_name: Glucuronic acid; parent_key: DB00304.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET00569; right_drugbank_name: Estrone glucuronide; parent_key: DB00655.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET01662; right_drugbank_name: 6beta-estrone; parent_key: DB00655.", + "sequence: 1; left_drugbank_id: DB00731; left_drugbank_name: Nateglinide; right_drugbank_id: DBMET01325; right_drugbank_name: Nateglinide glucuronide and isomers (M4/M5/M6); parent_key: DB00731.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET00616; right_drugbank_name: 4-Hydroxyestrone sulfate; parent_key: DB00655.", + "sequence: 2; left_drugbank_id: DBMET00491; left_drugbank_name: Estradiol; right_drugbank_id: DBMET00490; right_drugbank_name: Estrone; parent_key: DB00624.", + "sequence: 2; left_drugbank_id: DBMET01020; left_drugbank_name: (R)-MHD; right_drugbank_id: DBMET02804; right_drugbank_name: cis-10,11-dihydro-10,11-dihydroxycarbamazepine; parent_key: DB00776.", + "sequence: 2; left_drugbank_id: DBMET01423; left_drugbank_name: monohydroxy-bendamustine (bendamustine metabolite HP1); right_drugbank_id: DBMET01424; right_drugbank_name: dihydroxy-bendamustine (bendamustine metabolite HP2); parent_key: DB06769.", + "sequence: 1; left_drugbank_id: DB00655; left_drugbank_name: Estrone; right_drugbank_id: DBMET01659; right_drugbank_name: 2-OH-estrone; parent_key: DB00655.", + "sequence: 1; left_drugbank_id: DB04574; left_drugbank_name: Estrone sulfate; right_drugbank_id: DBMET00490; right_drugbank_name: Estrone; parent_key: DB04574." + ] + }, + { + "example_idx": 55, + "anchor_id": 4769626424237791914, + "positive_id": 8375506503587975644, + "join_paths": [ + [ + 14, + 6, + 0.361328125 + ], + [ + 11, + 6, + 0.357421875 + ], + [ + 5, + 49, + 0.34765625 + ], + [ + 3, + 6, + 0.341796875 + ], + [ + 11, + 45, + 0.3359375 + ] + ], + "rows": [ + "BACKGROUND: Fluorouracil (FU) is an antimetabolite with activity against numerous types of neoplasms, including those of the breast, esophagus, larynx, and gastrointestinal and genitourinary tracts.", + "Systemic toxicity, including neutropenia, stomatitis, and diarrhea, often occur due to cytotoxic nonselectivity.", + "Capecitabine was developed as a prodrug of FU, with the goal of improving tolerability and intratumor drug concentrations through tumor-specific conversion to the active drug.", + "OBJECTIVES: The purpose of this article is to review the available information on capecitabine with respect to clinical pharmacology, mechanism of action, pharmacokinetic and pharmacodynamic properties, clinical efficacy for breast and colorectal cancer adverse-effect profile, documented drug interactions, dosage and administration, and future directions of ongoing research.", + "METHODS: Relevant English-language literature was identified through searches of PubMed (1966 to August 2004), International Pharmaceutical Abstracts (1977 to August 2004), and the Proceedings of the American Society of Clinical Oncology (January 1995 to August 2004).", + "Search terms included capecitabine, Xeloda, breast cancer, and colorectal cancer.", + "The references of the identified articles were reviewed for additional sources.", + "In addition, product information was obtained from Roche Pharmaceuticals.", + "Studies from the identified literature that addressed this article's objectives were selected for review, with preference given to Phase II/III trials.", + "RESULTS: Capecitabine is an oral prodrug that is converted to its only active metabolite, FU, by thymidine phosphorylase.", + "Higher levels of this enzyme are found in several tumors and the liver, compared with normal healthy tissue.", + "In adults, capecitabine has a bioavailability of approximately 100% with a Cmax of 3.9 mg/L, Tmax of 1.5 to 2 hr, and AUC of 5.96 mg.h/L.", + "The predominant route of elimination is renal, and dosage reduction of 75% is recommended in patients with creatinine clearance (CrCl) of 30 to 50 mL/min.", + "The drug is contraindicated if CrCl is < 30 mL/min.", + "Capecitabine has shown varying degrees of efficacy with acceptable tolerability in numerous cancers including prostate, renal cell, ovarian, and pancreatic, with the largest amount of evidence in metastatic breast and colorectal cancer.", + "Single-agent capecitabine was compared with IV FU/leucovorin (LV) using the bolus Mayo Clinic regimen in 2 Phase III trials as first-line treatment for patients with metastatic colorectal cancer.", + "Overall response rate (RR) favored the capecitabine arm (26% vs 17%, P < 0.001); however, this did not translate into a difference in time to progression (TTP) (4.6 months vs 4.7 months) or overall survival (OS) (12.9 months vs 12.8 months).", + "In Phase II noncomparative trials, combinations of capecitabine with oxaliplatin or irinotecan have produced results similar to regimens combining FU/LV with the same agents in patients with colorectal cancer.", + "In metastatic breast cancer patients who had received prior treatment with an anthracycline-based regimen, a Phase III trial comparing the combination of capecitabine with docetaxel versus docetaxel alone demonstrated superior objective tumor RR (42% vs 30%, P = 0.006), median TTP (6.1 months vs 4.2 months, P < 0.001), and median OS (14.5 months vs 11.5 months, P = 0.013) with the combination treatment.", + "Noncomparative Phase II studies have also supported efficacy in patients with metastatic breast cancer pretreated with both anthracyclines and taxanes, yielding an overall RR of 15% to 29% and median OS of 9.4 to 15.2 months.", + "The most common dose-limiting adverse effects associated with capecitabine monotherapy are hyperbilirubinemia, diarrhea, and hand-foot syndrome.", + "Myelosuppression, fatigue and weakness, abdominal pain, and nausea have also been reported.", + "Compared with bolus FU/LV, capecitabine was associated with more hand-foot syndrome but less stomatitis, alopecia, neutropenia requiring medical management, diarrhea, and nausea.", + "Capecitabine has been reported to increase serum phenytoin levels and the international normalized ratio in patients receiving concomitant phenytoin and warfarin, respectively.", + "The dose of capecitabine approved by the US Food and Drug Administration (FDA) for both metastatic colorectal and breast cancer is 1250 Mg/M2 given orally twice per day, usually separated by 12 hours for the first 2 weeks of every 3-week cycle.", + "CONCLUSIONS: Capecitabine is currently approved by the FDA for use as first-line therapy in patients with metastatic colorectal cancer when single-agent fluoropyrimidine therapy is preferred.", + "The drug is also approved for use as (1) a single agent in metastatic breast cancer patients who are resistant to both anthracycline- and paclitaxel-based regimens or in whom further anthracycline treatment is contra indicated and (2) in combination with docetaxel after failure of prior anthracycline-based chemotherapy.", + "Single-agent and combination regimens have also shown benefits in patients with prostate, pancreatic, renal cell, and ovarian cancers.", + "Improved tolerability and comparable efficacy compared with IV FU/LV in addition to oral administration make capecitabine an attractive option for the treatment of several types of cancers as well as the focus of future trials.", + "Animals\nAntimetabolites, Antineoplastic\nCapecitabine\nClinical Trials as Topic\nDeoxycytidine\nFluorouracil\nHumans\nNeoplasms\nProdrugs" + ], + "sentences": [ + "name: Ecansya; ingredients: Capecitabine; parent_key: DB01101.", + "name: Taro-capecitabine; ingredients: Capecitabine; parent_key: DB01101.", + "name: Phenytoin Sodium Injection USP; ingredients: Phenytoin; parent_key: DB00252.", + "name: Phenytoin Sodium; ingredients: Phenytoin; parent_key: DB00252.", + "name: Phenytoin Soidum Injection USP; ingredients: Phenytoin; parent_key: DB00252.", + "name: Phenytoin ER; ingredients: Phenytoin; parent_key: DB00252.", + "name: Capecitabine; ingredients: Capecitabine; parent_key: DB01101.", + "name: Dilantin-30 Suspension; ingredients: Phenytoin; parent_key: DB00252.", + "name: Capecitabine Sun; ingredients: Capecitabine; parent_key: DB01101.", + "name: Care One Hemorrhoidal; ingredients: Cocoa butter + Phenylephrine + Shark liver oil; parent_key: DB11088.", + "name: Dilantin W Phenobarbital 30mg Cap; ingredients: Phenobarbital + Phenytoin; parent_key: DB00252.", + "name: Dilantin Inj 50mg/ml; ingredients: Phenytoin; parent_key: DB00252.", + "name: Phenytek; ingredients: Phenytoin; parent_key: DB00252.", + "name: Dilantin W Phenobarbital 15mg; ingredients: Phenobarbital + Phenytoin; parent_key: DB00252.", + "name: Phenytoin; ingredients: Phenytoin; parent_key: DB00252.", + "name: Phenytoin Infatabs; ingredients: Phenytoin; parent_key: DB00252.", + "name: Apo-phenytoin Sodium; ingredients: Phenytoin; parent_key: DB00252.", + "name: Capecitabine 500mg; ingredients: Capecitabine; parent_key: DB01101.", + "name: Capecitabine Tablets, 150 mg; ingredients: Capecitabine; parent_key: DB01101.", + "name: Dilantin; ingredients: Phenytoin; parent_key: DB00252.", + "name: Formulation R Hemorrhoidal Ointment; ingredients: Mineral oil + Petrolatum + Phenylephrine + Shark liver oil; parent_key: DB11057.", + "name: Capecitabine Teva; ingredients: Capecitabine; parent_key: DB01101.", + "name: OHUI SUN SCIENCE Perfect Sunblock Blue EX plus; ingredients: Bemotrizinol + Ensulizole + Octisalate + Polysilicone-15 + Titanium dioxide; parent_key: DB09536.", + "name: Teva-capecitabine; ingredients: Capecitabine; parent_key: DB01101.", + "name: Dilantin Kapseals; ingredients: Phenytoin; parent_key: DB00252.", + "name: Family wellness hemorrhoidal; ingredients: Mineral oil + Petrolatum + Phenylephrine + Shark liver oil; parent_key: DB11088.", + "name: Dilantin W Phenobarbital 30mg Cap; ingredients: Phenobarbital + Phenytoin; parent_key: DB01174.", + "name: Apo-capecitabine; ingredients: Capecitabine; parent_key: DB01101.", + "name: Dilantin-125; ingredients: Phenytoin; parent_key: DB00252.", + "name: Dilantin Infatabs; ingredients: Phenytoin; parent_key: DB00252.", + "name: Capecitabine Accord; ingredients: Capecitabine; parent_key: DB01101.", + "name: Dilantin W Phenobarbital 15mg; ingredients: Phenobarbital + Phenytoin; parent_key: DB01174.", + "name: Sandoz Capecitabine; ingredients: Capecitabine; parent_key: DB01101.", + "name: Novo-phenytoin Cap 100mg; ingredients: Phenytoin; parent_key: DB00252.", + "name: Prevnar 13; ingredients: Streptococcus pneumoniae type 1 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 14 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 18c capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 19a capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 19f capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 23f capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 3 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 4 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 5 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 6a capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 6b capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 7f capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 9v capsular polysaccharide diphtheria crm197 protein conjugate antigen; parent_key: DB10297.", + "name: Jantoven; ingredients: Warfarin; parent_key: DB00682.", + "name: Phenytoin Sodium Extended; ingredients: Phenytoin; parent_key: DB00252.", + "name: Phenytoin Sodium Injection, USP; ingredients: Phenytoin; parent_key: DB00252.", + "name: Dilantin-125 Suspension; ingredients: Phenytoin; parent_key: DB00252.", + "name: Capecitabine Medac; ingredients: Capecitabine; parent_key: DB01101.", + "name: Capecitabine Tablets, 500 mg; ingredients: Capecitabine; parent_key: DB01101.", + "name: Taro-phenytoin; ingredients: Phenytoin; parent_key: DB00252.", + "name: Equate Hemorrhoidal; ingredients: Mineral oil + Petrolatum + Phenylephrine + Shark liver oil; parent_key: DB11057.", + "name: Fluarix Quadrivalent 2018/2019; ingredients: Influenza A virus A/Singapore/gp1908/2015 IVR-180 (H1N1) antigen (formaldehyde inactivated) + Influenza A virus A/Singapore/INFIMH-16-0019/2016 NIB-104 (H3N2) antigen (formaldehyde inactivated) + Influenza B virus B/Maryland/15/2016 BX-69A antigen (formaldehyde inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (formaldehyde inactivated); parent_key: DB14558.", + "name: Hemorrhoidal Rectal; ingredients: Cocoa butter + Phenylephrine + Shark liver oil; parent_key: DB11088.", + "name: Capecitabine 150mg; ingredients: Capecitabine; parent_key: DB01101.", + "name: Ach-capecitabine; ingredients: Capecitabine; parent_key: DB01101.", + "name: Extended Phenytoin Sodium; ingredients: Phenytoin; parent_key: DB00252.", + "name: Xenaderm; ingredients: Balsam of Peru + Castor oil + Trypsin; parent_key: DB11113.", + "name: Xeloda; ingredients: Capecitabine; parent_key: DB01101." + ] + }, + { + "example_idx": 56, + "anchor_id": 2735206562938581392, + "positive_id": 16901547675328997114, + "join_paths": [ + [ + 0, + 19, + 0.337890625 + ], + [ + 0, + 47, + 0.333984375 + ], + [ + 0, + 18, + 0.33203125 + ], + [ + 0, + 8, + 0.328125 + ], + [ + 0, + 25, + 0.326171875 + ] + ], + "rows": [ + "The channel of NMDA receptors is blocked by a wide variety of drugs.", + "NMDA receptor channel blockers include drugs of abuse that induce psychotic behavior, such as phencyclidine, and drugs with wide therapeutic utility, such as amantadine and memantine.", + "We describe here the molecular mechanism of amantadine inhibition.", + "In contrast to most other described channel-blocking molecules, amantadine causes the channel gate of NMDA receptors to close more quickly.", + "Our results confirm that amantadine binding inhibits current flow through NMDA receptor channels but show that its main inhibitory action at pharmaceutically relevant concentrations results from stabilization of closed states of the channel.", + "The surprising variation in the clinical utility of NMDA channel blockers may in part derive from their diverse effects on channel gating.", + "Amantadine\nAnalgesics, Non-Narcotic\nAnimals\nCells, Cultured\nCerebral Cortex\nDose-Response Relationship, Drug\nDrug Interactions\nElectric Stimulation\nEmbryo, Mammalian\nGlycine\nHumans\nInhibitory Concentration 50\nIon Channel Gating\nIon Channels\nNeural Inhibition\nNeurons\nPatch-Clamp Techniques\nRats\nReceptors, N-Methyl-D-Aspartate\nTime Factors\nTransfection" + ], + "sentences": [ + "id: BE0010000; name: Muscle nicotinic acetylcholine receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB00674.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB00697.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: no; position: 21; parent_key: DB14185.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB13025.", + "id: BE0003687; name: Penicillin-binding protein 1B; organism: Pseudomonas aeruginosa; known_action: yes; position: 5; parent_key: DB01329.", + "id: BE0000353; name: Acid-sensing ion channel 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00594.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB00431.", + "id: BE0000365; name: Glutamate receptor ionotropic, NMDA 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB00454.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00333.", + "id: BE0004852; name: Glutamate (NMDA) receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB09409.", + "id: BE0000641; name: Glutamate receptor ionotropic, NMDA 3A; organism: Humans; known_action: unknown; position: 41; parent_key: DB00142.", + "id: BE0009793; name: Kainate receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB00273.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB13345.", + "id: BE0003786; name: Low molecular weight phosphotyrosine protein phosphatase; organism: Humans; known_action: unknown; parent_key: DB00173.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 16; parent_key: DB01224.", + "id: BE0000417; name: Glutamate receptor ionotropic, NMDA 2B; organism: Humans; known_action: yes; position: 1; parent_key: DB00949.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09194.", + "id: BE0002342; name: Metabotropic glutamate receptor 3; organism: Humans; known_action: unknown; parent_key: DB05096.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: yes; position: 14; parent_key: DB00193.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB11823.", + "id: BE0000417; name: Glutamate receptor ionotropic, NMDA 2B; organism: Humans; known_action: unknown; parent_key: DB05956.", + "id: BE0000365; name: Glutamate receptor ionotropic, NMDA 1; organism: Humans; known_action: unknown; parent_key: DB04620.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: no; position: 7; parent_key: DB00934.", + "id: BE0000147; name: Receptor-type tyrosine-protein kinase FLT3; organism: Humans; known_action: unknown; parent_key: DB12742.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 6; parent_key: DB01175.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB04896.", + "id: BE0004851; name: Schistosome calcium ion (Ca2+) channels; organism: Schistosoma; known_action: yes; position: 1; parent_key: DB01058.", + "id: BE0000417; name: Glutamate receptor ionotropic, NMDA 2B; organism: Humans; known_action: unknown; position: 2; parent_key: DB00454.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 7; parent_key: DB01186.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB09195.", + "id: BE0000760; name: Glutamate receptor ionotropic, NMDA 2A; organism: Humans; known_action: unknown; position: 10; parent_key: DB06151.", + "id: BE0000454; name: Glutamate receptor ionotropic, NMDA 2C; organism: Humans; known_action: unknown; position: 35; parent_key: DB00142.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: no; position: 3; parent_key: DB00433.", + "id: BE0000454; name: Glutamate receptor ionotropic, NMDA 2C; organism: Humans; known_action: yes; parent_key: DB01520.", + "id: BE0000678; name: Acid-sensing ion channel 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB00594.", + "id: BE0004852; name: Glutamate (NMDA) receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00659.", + "id: BE0000641; name: Glutamate receptor ionotropic, NMDA 3A; organism: Humans; known_action: yes; parent_key: DB03575.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 10; parent_key: DB08922.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB11273.", + "id: BE0004643; name: Penicillin-binding protein 3; organism: Streptococcus pneumoniae; known_action: yes; position: 3; parent_key: DB00415.", + "id: BE0000365; name: Glutamate receptor ionotropic, NMDA 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB01043.", + "id: BE0000454; name: Glutamate receptor ionotropic, NMDA 2C; organism: Humans; known_action: unknown; position: 4; parent_key: DB00454.", + "id: BE0000451; name: 5-hydroxytryptamine receptor 2A; organism: Humans; known_action: unknown; position: 1; parent_key: DB08927.", + "id: BE0000417; name: Glutamate receptor ionotropic, NMDA 2B; organism: Humans; known_action: yes; position: 7; parent_key: DB01956.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB09202.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 11; parent_key: DB01645.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; parent_key: DB04630.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00874.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 11; parent_key: DB01239.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB00397." + ] + }, + { + "example_idx": 57, + "anchor_id": 3673286136820377737, + "positive_id": 12832398310352133127, + "join_paths": [ + [ + 13, + 12, + 0.2255859375 + ], + [ + 13, + 6, + 0.2216796875 + ], + [ + 13, + 33, + 0.2177734375 + ], + [ + 13, + 41, + 0.2119140625 + ], + [ + 13, + 24, + 0.2109375 + ] + ], + "rows": [ + "The objective of this work was to design an acyclovir prodrug that would utilize the human apical sodium-dependent bile acid transporter (hASBT) and enhance acyclovir oral bioavailability.", + "Using each chenodeoxycholate, deoxycholate, cholate, and ursodeoxycholate, four bile acid prodrugs of acyclovir were synthesized, where acyclovir was conjugated to a bile acid via a valine linker.", + "The affinity of the prodrug for hASBT was determined through inhibition of taurocholate uptake by COS-7 cells transfected with hASBT (hASBT-COS).", + "The prodrug with the highest inhibitory affinity was further evaluated in vitro and in vivo.", + "The prodrug acyclovir valylchenodeoxycholate yielded the highest affinity for hASBT (Ki = 35 microM), showing that chenodeoxycholate is the free bile acid with the greatest affinity for hASBT.", + "Acyclovir valylchenodeoxycholate's affinity was similar to that of cholic acid (Ki = 25 microM).", + "Further characterization showed that acyclovir was catalytically liberated from acyclovir valylchenode-oxycholate by esterase.", + "Relative to cellular uptake studies of acyclovir alone, the cellular uptake from the prodrug resulted in a 16-fold greater acyclovir accumulation within hASBT-COS cells, indicating enhanced permeation properties of the prodrug.", + "Enhanced permeability was due to hASBT-mediated uptake and increased passive permeability.", + "The extent of acyclovir uptake in the presence of sodium was 1.4-fold greater than the extent of passive prodrug uptake in the absence of sodium (p = 0.02), indicating translocation of the prodrug by hASBT.", + "The prodrug also exhibited an almost 12-fold enhanced passive permeability, relative to acyclovir's passive permeability.", + "Oral administration of acyclovir valylchenodeoxycholate to rats resulted in a 2-fold increase in the bioavailability of acyclovir, compared to the bioavailability after administration of acyclovir alone.", + "Results indicate that a bile acid prodrug strategy may be useful in improving the oral bioavailability of intestinal permeability-limited compounds.", + "Acyclovir\nAdministration, Oral\nAnimals\nAntiviral Agents\nBile Acids and Salts\nBiological Availability\nBiological Transport\nCOS Cells\nChenodeoxycholic Acid\nChlorocebus aethiops\nKinetics\nProdrugs" + ], + "sentences": [ + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Pidotimod which could result in a higher serum level.; parent_key: DB11364.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Arformoterol which could result in a higher serum level.; parent_key: DB01274.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Budesonide which could result in a higher serum level.; parent_key: DB01222.", + "drugbank-id: DB02659; name: Cholic Acid; description: The excretion of Estradiol can be decreased when combined with Cholic Acid.; parent_key: DB00783.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Magnesium carbonate which could result in a higher serum level.; parent_key: DB09481.", + "drugbank-id: DB00787; name: Acyclovir; description: The risk or severity of adverse effects can be increased when Saquinavir is combined with Acyclovir.; parent_key: DB01232.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Acyclovir can be increased when combined with Ritonavir.; parent_key: DB00503.", + "drugbank-id: DB00787; name: Acyclovir; description: Bendazac may decrease the excretion rate of Acyclovir which could result in a higher serum level.; parent_key: DB13501.", + "drugbank-id: DB10962; name: Agrostis stolonifera pollen; description: The risk of a hypersensitivity reaction to Agrostis stolonifera pollen is increased when it is combined with Atenolol.; parent_key: DB00335.", + "drugbank-id: DB06695; name: Dabigatran etexilate; description: Dabigatran etexilate may increase the anticoagulant activities of Anistreplase.; parent_key: DB00029.", + "drugbank-id: DB00787; name: Acyclovir; description: Naproxen may decrease the excretion rate of Acyclovir which could result in a higher serum level.; parent_key: DB00788.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Acyclovir can be decreased when combined with Imatinib.; parent_key: DB00619.", + "drugbank-id: DB00787; name: Acyclovir; description: The excretion of Acyclovir can be decreased when combined with Favipiravir.; parent_key: DB12466.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Maprotiline which could result in a higher serum level.; parent_key: DB00934.", + "drugbank-id: DB00787; name: Acyclovir; description: Potassium may increase the excretion rate of Acyclovir which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB14500.", + "drugbank-id: DB00787; name: Acyclovir; description: The risk or severity of adverse effects can be increased when Chlorpheniramine is combined with Acyclovir.; parent_key: DB01114.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Bromazepam which could result in a higher serum level.; parent_key: DB01558.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Nedaplatin which could result in a higher serum level.; parent_key: DB13145.", + "drugbank-id: DB00789; name: Gadopentetic acid; description: Liothyronine may decrease the excretion rate of Gadopentetic acid which could result in a higher serum level.; parent_key: DB00279.", + "drugbank-id: DB00787; name: Acyclovir; description: The excretion of Acyclovir can be decreased when combined with Cilastatin.; parent_key: DB01597.", + "drugbank-id: DB12007; name: Isoflavone; description: Leuprolide may decrease the excretion rate of Isoflavone which could result in a higher serum level.; parent_key: DB00007.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Canagliflozin which could result in a higher serum level.; parent_key: DB08907.", + "drugbank-id: DB00787; name: Acyclovir; description: Cimicoxib may decrease the excretion rate of Acyclovir which could result in a higher serum level.; parent_key: DB05095.", + "drugbank-id: DB08824; name: Ioflupane I-123; description: Desmopressin may decrease the excretion rate of Ioflupane I-123 which could result in a higher serum level.; parent_key: DB00035.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Acyclovir can be decreased when combined with Interferon alfacon-1.; parent_key: DB00069.", + "drugbank-id: DB00787; name: Acyclovir; description: Mebutizide may increase the excretion rate of Acyclovir which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB13430.", + "drugbank-id: DB04914; name: G17DT; description: The therapeutic efficacy of G17DT can be decreased when used in combination with Peginterferon alfa-2a.; parent_key: DB00008.", + "drugbank-id: DB00787; name: Acyclovir; description: Flomoxef may decrease the excretion rate of Acyclovir which could result in a higher serum level.; parent_key: DB11935.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Octinoxate which could result in a higher serum level.; parent_key: DB09496.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Propentofylline can be decreased when combined with Acyclovir.; parent_key: DB06479.", + "drugbank-id: DB09154; name: Sodium citrate; description: The therapeutic efficacy of Sodium citrate can be decreased when used in combination with Cefazolin.; parent_key: DB01327.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Acyclovir can be decreased when combined with Selegiline.; parent_key: DB01037.", + "drugbank-id: DB00286; name: Conjugated estrogens; description: Acyclovir may decrease the excretion rate of Conjugated estrogens which could result in a higher serum level.; parent_key: DB00787.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Acyclovir can be increased when combined with Cyproterone acetate.; parent_key: DB04839.", + "drugbank-id: DB09133; name: Iothalamic acid; description: Tositumomab may decrease the excretion rate of Iothalamic acid which could result in a higher serum level.; parent_key: DB00081.", + "drugbank-id: DB00787; name: Acyclovir; description: Cyclosporine may decrease the excretion rate of Acyclovir which could result in a higher serum level.; parent_key: DB00091.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Acyclovir can be increased when combined with Insulin tregopil.; parent_key: DB11568.", + "drugbank-id: DB00787; name: Acyclovir; description: Pirprofen may decrease the excretion rate of Acyclovir which could result in a higher serum level.; parent_key: DB13722.", + "drugbank-id: DB10964; name: Lolium perenne subsp. multiflorum pollen; description: The risk of a hypersensitivity reaction to Lolium perenne subsp. multiflorum pollen is increased when it is combined with Indenolol.; parent_key: DB08952.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Genistein can be decreased when combined with Acyclovir.; parent_key: DB01645.", + "drugbank-id: DB00787; name: Acyclovir; description: Cefotiam may decrease the excretion rate of Acyclovir which could result in a higher serum level.; parent_key: DB00229.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Acyclovir can be decreased when combined with Interferon alfa.; parent_key: DB05258.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Verapamil which could result in a higher serum level.; parent_key: DB00661.", + "drugbank-id: DB00787; name: Acyclovir; description: Acetazolamide may increase the excretion rate of Acyclovir which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB00819.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Iodixanol which could result in a higher serum level.; parent_key: DB01249.", + "drugbank-id: DB00787; name: Acyclovir; description: The metabolism of Acefylline can be decreased when combined with Acyclovir.; parent_key: DB13573.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Peginesatide which could result in a higher serum level.; parent_key: DB08894.", + "drugbank-id: DB00787; name: Acyclovir; description: The risk or severity of adverse effects can be increased when Acyclovir is combined with Spermine.; parent_key: DB00127.", + "drugbank-id: DB00787; name: Acyclovir; description: The excretion of Acyclovir can be decreased when combined with Tafenoquine.; parent_key: DB06608.", + "drugbank-id: DB00787; name: Acyclovir; description: Acyclovir may decrease the excretion rate of Tamsulosin which could result in a higher serum level.; parent_key: DB00706." + ] + }, + { + "example_idx": 58, + "anchor_id": 7595204363647566670, + "positive_id": 9881446874348840513, + "join_paths": [ + [ + 0, + 25, + 0.197265625 + ], + [ + 0, + 0, + 0.171875 + ], + [ + 0, + 40, + 0.1708984375 + ], + [ + 0, + 4, + 0.1669921875 + ], + [ + 0, + 5, + 0.166015625 + ] + ], + "rows": [ + "A Pseudomonas aeruginosa strain expresses an extended-spectrum beta-lactamase, GES-9, which differs from GES-1 by a Gly243Ser substitution, is inhibited by clavulanic acid and imipenem, and hydrolyzes aztreonam.", + "The bla(GES-9) gene was located inside a class 1 integron structure containing two copies of a novel insertion sequence belonging to the IS1111 family.", + "Amino Acid Sequence\nAmino Acid Substitution\nAnti-Bacterial Agents\nAztreonam\nBase Sequence\nDNA Transposable Elements\nHumans\nIntegrons\nKinetics\nMicrobial Sensitivity Tests\nMolecular Sequence Data\nPseudomonas Infections\nPseudomonas aeruginosa\nbeta-Lactam Resistance\nbeta-Lactamases" + ], + "sentences": [ + "id: BE0001430; name: Beta-lactamase; organism: Enterobacter cloacae; known_action: yes; position: 5; parent_key: DB09060.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB08551.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02094.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB03531.", + "id: BE0001430; name: Beta-lactamase; organism: Enterobacter cloacae; known_action: unknown; parent_key: DB03970.", + "id: BE0001430; name: Beta-lactamase; organism: Enterobacter cloacae; known_action: unknown; parent_key: DB02816.", + "id: BE0002718; name: Beta-lactamase; organism: Escherichia coli; known_action: unknown; position: 1; parent_key: DB07865.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03658.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02627.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB03793.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02588.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB08623.", + "id: BE0000009; name: Alcohol dehydrogenase class-3; organism: Humans; known_action: unknown; parent_key: DB03704.", + "id: BE0000988; name: Beta-secretase 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB07737.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB08573.", + "id: BE0003366; name: DNA-directed RNA polymerase subunit alpha; organism: Thermus thermophilus; known_action: unknown; position: 1; parent_key: DB08226.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; position: 1; parent_key: DB07979.", + "id: BE0001426; name: Beta-lactamase 2; organism: Bacillus cereus; known_action: unknown; parent_key: DB02153.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; position: 1; parent_key: DB01351.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB03225.", + "id: BE0004566; name: L-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB03147.", + "id: BE0001444; name: Beta-lactamase; organism: Citrobacter freundii; known_action: yes; parent_key: DB00355.", + "id: BE0000143; name: Tubulin beta chain; organism: Humans; known_action: yes; position: 2; parent_key: DB01179.", + "id: BE0002718; name: Beta-lactamase; organism: Escherichia coli; known_action: unknown; position: 1; parent_key: DB07808.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB02838.", + "id: BE0008647; name: Extended-spectrum beta-lactamase PER-1; organism: Pseudomonas aeruginosa; known_action: yes; position: 12; parent_key: DB09060.", + "id: BE0001426; name: Beta-lactamase 2; organism: Bacillus cereus; known_action: unknown; parent_key: DB04272.", + "id: BE0002718; name: Beta-lactamase; organism: Escherichia coli; known_action: unknown; position: 3; parent_key: DB08551.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; position: 1; parent_key: DB02988.", + "id: BE0004566; name: L-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB04272.", + "id: BE0004566; name: L-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB04166.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB04166.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB07057.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02797.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB08336.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; position: 2; parent_key: DB07824.", + "id: BE0000675; name: Anti-Muellerian hormone type-2 receptor; organism: Humans; known_action: unknown; parent_key: DB00171.", + "id: BE0003573; name: Major histocompatibility complex class I-related gene protein; organism: Humans; known_action: yes; position: 1; parent_key: DB00098.", + "id: BE0004566; name: L-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB03214.", + "id: BE0004769; name: Y+L amino acid transporter 1; organism: Humans; known_action: yes; position: 2; parent_key: DB13146.", + "id: BE0001430; name: Beta-lactamase; organism: Enterobacter cloacae; known_action: yes; position: 9; parent_key: DB12377.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB03147.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04360.", + "id: BE0009515; name: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma; organism: Humans; known_action: unknown; position: 247; parent_key: DB12010.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03437.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02247.", + "id: BE0001358; name: Beta-lactamase; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB08731.", + "id: BE0001024; name: Troponin C, slow skeletal and cardiac muscles; organism: Humans; known_action: yes; position: 4; parent_key: DB01373.", + "id: BE0001898; name: Heat shock protein HSP 90-beta; organism: Humans; known_action: unknown; position: 1; parent_key: DB08464.", + "id: BE0000283; name: Tubulin beta chain; organism: Yeast; known_action: yes; position: 1; parent_key: DB00400." + ] + }, + { + "example_idx": 59, + "anchor_id": 15820792523176114571, + "positive_id": 8786494340645514498, + "join_paths": [ + [ + 4, + 16, + 0.2138671875 + ], + [ + 4, + 22, + 0.2119140625 + ], + [ + 4, + 19, + 0.2080078125 + ], + [ + 4, + 18, + 0.2021484375 + ], + [ + 4, + 35, + 0.197265625 + ] + ], + "rows": [ + "Mutations at position 306 of embB (embB306) have been proposed as a marker for ethambutol resistance in Mycobacterium tuberculosis; however, recent reports of embB306 mutations in ethambutol-susceptible isolates caused us to question the biological role of this mutation.", + "We tested 1,020 clinical M. tuberculosis isolates with different drug susceptibility patterns and of different geographical origins for associations between embB306 mutations, drug resistance patterns, and major genetic group.", + "One hundred isolates (10%) contained a mutation in embB306; however, only 55 of these mutants were ethambutol resistant.", + "Mutations in embB306 could not be uniquely associated with any particular type of drug resistance and were found in all three major genetic groups.", + "A striking association was observed between these mutations and resistance to any drug (P < 0.001), and the association between embB306 mutations and resistance to increasing numbers of drugs was highly significant (P < 0.001 for trend).", + "We examined the association between embB306 mutations and IS6110 clustering (as a proxy for transmission) among all drug-resistant isolates.", + "Mutations in embB306 were significantly associated with clustering by univariate analysis (odds ratio, 2.44; P = 0.004).", + "In a multivariate model that also included mutations in katG315, katG463, gyrA95, and kasA269, only mutations in embB306 (odds ratio, 2.14; P = 0.008) and katG315 (odds ratio, 1.99; P = 0.015) were found to be independently associated with clustering.", + "In conclusion, embB306 mutations do not cause classical ethambutol resistance but may predispose M. tuberculosis isolates to the development of resistance to increasing numbers of antibiotics and may increase the ability of drug-resistant isolates to be transmitted between subjects.", + "Antitubercular Agents\nBase Sequence\nCluster Analysis\nDNA, Bacterial\nDrug Resistance, Bacterial\nEthambutol\nGenes, Bacterial\nMicrobial Sensitivity Tests\nMolecular Sequence Data\nMultigene Family\nMultivariate Analysis\nMutation\nMycobacterium tuberculosis\nPhylogeny" + ], + "sentences": [ + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00854.", + "id: BE0009167; name: Multidrug resistance protein; organism: Plasmodium falciparum (isolate FC27 / Papua New Guinea); known_action: unknown; position: 84; parent_key: DB11638.", + "id: BE0008685; name: Natural resistance-associated macrophage protein 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB15598.", + "id: BE0008666; name: DMD-001 gene (exon 51 target site); organism: Humans; known_action: yes; position: 1; parent_key: DB06014.", + "id: BE0005802; name: G-protein coupled receptor 55; organism: Humans; known_action: unknown; position: 15; parent_key: DB14011.", + "id: BE0009711; name: Bacterial beta-lactamase enzymes; known_action: unknown; position: 2; parent_key: DB00766.", + "id: BE0000623; name: Tyrosine-protein phosphatase non-receptor type 1; organism: Humans; known_action: unknown; parent_key: DB04142.", + "id: BE0002357; name: Voltage-dependent L-type calcium channel subunit alpha-1F; organism: Humans; known_action: yes; position: 11; parent_key: DB04855.", + "id: BE0002903; name: Bacterial hemoglobin; organism: Vitreoscilla stercoraria; known_action: unknown; parent_key: DB03366.", + "id: BE0001395; name: Bacterial leucyl aminopeptidase; organism: Vibrio proteolyticus; known_action: unknown; parent_key: DB01980.", + "id: BE0009370; name: Thiol groups; organism: Humans; known_action: yes; position: 1; parent_key: DB13960.", + "id: BE0002149; name: Proline synthase co-transcribed bacterial homolog protein; organism: Humans; known_action: unknown; position: 33; parent_key: DB00114.", + "id: BE0001395; name: Bacterial leucyl aminopeptidase; organism: Vibrio proteolyticus; known_action: unknown; parent_key: DB02664.", + "id: BE0004833; name: Bacterial outer membrane; organism: Bacteria; known_action: yes; position: 1; parent_key: DB01111.", + "id: BE0009716; name: Cyd operon, Mycobacterium tuberculosis; organism: Mycobacterium tuberculosis; known_action: unknown; position: 7; parent_key: DB05154.", + "id: BE0001226; name: Major NAD(P)H-flavin oxidoreductase; organism: Vibrio fischeri; known_action: unknown; parent_key: DB03247.", + "id: BE0003639; name: Multidrug resistance-associated protein 5; organism: Humans; known_action: unknown; position: 7; parent_key: DB14635.", + "id: BE0005802; name: G-protein coupled receptor 55; organism: Humans; known_action: unknown; position: 20; parent_key: DB14009.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 11; parent_key: DB06176.", + "id: BE0003640; name: Multidrug resistance-associated protein 6; organism: Humans; known_action: unknown; position: 1; parent_key: DB00171.", + "id: BE0004833; name: Bacterial outer membrane; organism: Bacteria; known_action: yes; position: 1; parent_key: DB00803.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: unknown; parent_key: DB00473.", + "id: BE0003639; name: Multidrug resistance-associated protein 5; organism: Humans; known_action: unknown; position: 3; parent_key: DB11672.", + "id: BE0002149; name: Proline synthase co-transcribed bacterial homolog protein; organism: Humans; known_action: unknown; parent_key: DB00172.", + "id: BE0004193; name: Bacterial regulatory protein, TetR family; organism: Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / JCM 1318 / LMG 3730 / NCIMB 10025); known_action: unknown; position: 2; parent_key: DB08167.", + "id: BE0005802; name: G-protein coupled receptor 55; organism: Humans; known_action: unknown; position: 1; parent_key: DB06155.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: yes; parent_key: DB01138.", + "id: BE0000420; name: Delta-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB01571.", + "id: BE0004833; name: Bacterial outer membrane; organism: Bacteria; known_action: yes; parent_key: DB00080.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB00171.", + "id: BE0001395; name: Bacterial leucyl aminopeptidase; organism: Vibrio proteolyticus; known_action: unknown; parent_key: DB03424.", + "id: BE0009695; name: Anaerobic bacterial DNA; known_action: unknown; position: 3; parent_key: DB00916.", + "id: BE0003120; name: Oxidoreductase, short chain dehydrogenase/reductase family; organism: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099); known_action: unknown; parent_key: DB03461.", + "id: BE0005802; name: G-protein coupled receptor 55; organism: Humans; known_action: unknown; position: 12; parent_key: DB09061.", + "id: BE0002226; name: Voltage-dependent N-type calcium channel subunit alpha-1B; organism: Humans; known_action: yes; position: 1; parent_key: DB06283.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB08855.", + "id: BE0000623; name: Tyrosine-protein phosphatase non-receptor type 1; organism: Humans; known_action: unknown; parent_key: DB02622.", + "id: BE0001817; name: Acriflavine resistance protein B; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03825.", + "id: BE0001817; name: Acriflavine resistance protein B; organism: Escherichia coli (strain K12); known_action: unknown; position: 6; parent_key: DB03619.", + "id: BE0001188; name: Multidrug resistance-associated protein 4; organism: Humans; known_action: unknown; position: 2; parent_key: DB00171.", + "id: BE0000864; name: Voltage-dependent T-type calcium channel subunit alpha-1H; organism: Humans; known_action: unknown; position: 6; parent_key: DB01023.", + "id: BE0004833; name: Bacterial outer membrane; organism: Bacteria; known_action: yes; position: 1; parent_key: DB00781.", + "id: BE0001105; name: Major prion protein; organism: Humans; known_action: unknown; position: 7; parent_key: DB00759.", + "id: BE0002347; name: Proteasome subunit beta type-1; organism: Humans; known_action: unknown; position: 8; parent_key: DB08515.", + "id: BE0001395; name: Bacterial leucyl aminopeptidase; organism: Vibrio proteolyticus; known_action: unknown; parent_key: DB02386.", + "id: BE0004833; name: Bacterial outer membrane; organism: Bacteria; known_action: yes; position: 1; parent_key: DB00878.", + "id: BE0005802; name: G-protein coupled receptor 55; organism: Humans; known_action: yes; position: 3; parent_key: DB11755.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; parent_key: DB04851.", + "id: BE0001817; name: Acriflavine resistance protein B; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04209.", + "id: BE0009205; name: Chloroquine resistance transporter; organism: Plasmodium falciparum; known_action: unknown; position: 123; parent_key: DB11638." + ] + }, + { + "example_idx": 60, + "anchor_id": 324757251990848346, + "positive_id": 7961512307329954953, + "join_paths": [ + [ + 8, + 20, + 0.328125 + ], + [ + 8, + 13, + 0.326171875 + ], + [ + 8, + 33, + 0.326171875 + ], + [ + 8, + 6, + 0.318359375 + ], + [ + 8, + 41, + 0.31640625 + ] + ], + "rows": [ + "The purpose of the present study was to explore the analgesic effects of the low voltage-activated T-type Ca2+ channel blockers ethosuximide, trimethadione, and mibefradil in persistent and acute nociceptive tests.", + "The anticonvulsant effects of the compounds were also determined in the intravenous pentylenetetrazol seizure model.", + "Following intraperitoneal administration, ethosuximide and trimethadione dose-dependently reversed capsaicin-induced mechanical hyperalgesia.", + "Similarly, the highest dose of mibefradil tested (30 microg, intracisternal) reversed capsaicin-induced mechanical hyperalgesia.", + "Ethosuximide and mibefradil produced statistically significant analgesic effects in both early and late phase formalin-induced behaviors and trimethadione reduced late phase behaviors.", + "Additionally, ethosuximide and trimethadione produced antinociceptive effects in the rat-tail flick reflex test.", + "In contrast, following intracisternal administration, mibefradil had no effect in the tail flick reflex test.", + "In addition, the anticonvulsants ethosuximide and trimethadione increased the doses of pentylenetetrazol required to produce both first twitch and clonic seizures.", + "In contrast however, mibefradil had no anticonvulsant effect.", + "The present results demonstrate that the clinically used anticonvulsants ethosuximide and trimethadione provide analgesic effects at doses, which are anticonvulsant.", + "Furthermore, the data further supports the idea that T-type Ca2+ channels may be important targets for treating persistent pain syndromes.", + "Animals\nAnticonvulsants\nBehavior, Animal\nCalcium Channel Blockers\nCalcium Channels, T-Type\nDose-Response Relationship, Drug\nEthosuximide\nHyperalgesia\nMale\nMibefradil\nPain Measurement\nPain Threshold\nRats\nRats, Sprague-Dawley\nTime Factors\nTrimethadione" + ], + "sentences": [ + "drugbank-id: DB01388; name: Mibefradil; description: Mibefradil may increase the hypotensive activities of Obinutuzumab.; parent_key: DB08935.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hyperkalemia can be increased when Mibefradil is combined with Certoparin.; parent_key: DB09261.", + "drugbank-id: DB10990; name: Haemophilus influenzae type B strain 20752 capsular polysaccharide tetanus toxoid conjugate antigen; description: The therapeutic efficacy of Haemophilus influenzae type B strain 20752 capsular polysaccharide tetanus toxoid conjugate antigen can be decreased when used in combination with Ruxolitinib.; parent_key: DB08877.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Simvastatin can be decreased when combined with Mibefradil.; parent_key: DB00641.", + "drugbank-id: DB10966; name: Sorghum bicolor subsp. drummondii pollen; description: The risk of a hypersensitivity reaction to Sorghum bicolor subsp. drummondii pollen is increased when it is combined with Propranolol.; parent_key: DB00571.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hyperkalemia can be increased when Mibefradil is combined with Quinaprilat.; parent_key: DB14217.", + "drugbank-id: DB01388; name: Mibefradil; description: Pregabalin may increase the arrhythmogenic activities of Mibefradil.; parent_key: DB00230.", + "drugbank-id: DB01388; name: Mibefradil; description: The therapeutic efficacy of Mibefradil can be decreased when used in combination with Guacetisal.; parent_key: DB13538.", + "drugbank-id: DB01353; name: Butobarbital; description: The risk or severity of adverse effects can be increased when Butobarbital is combined with Botulinum Toxin Type B.; parent_key: DB00042.", + "drugbank-id: DB01388; name: Mibefradil; description: Mibefradil may increase the arrhythmogenic activities of Digoxin.; parent_key: DB00390.", + "drugbank-id: DB01105; name: Sibutramine; description: The risk or severity of adverse effects can be increased when Botulinum Toxin Type B is combined with Sibutramine.; parent_key: DB00042.", + "drugbank-id: DB01388; name: Mibefradil; description: The serum concentration of Doxorubicin can be increased when it is combined with Mibefradil.; parent_key: DB00997.", + "drugbank-id: DB11856; name: Ligelizumab; description: The risk or severity of adverse effects can be increased when Cetuximab is combined with Ligelizumab.; parent_key: DB00002.", + "drugbank-id: DB01388; name: Mibefradil; description: Mibefradil may increase the arrhythmogenic activities of Lorcainide.; parent_key: DB13653.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Oxymorphone can be decreased when combined with Mibefradil.; parent_key: DB01192.", + "drugbank-id: DB01388; name: Mibefradil; description: The serum concentration of Ticagrelor can be increased when it is combined with Mibefradil.; parent_key: DB08816.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hypoglycemia can be increased when Mibefradil is combined with Carmegliptin.; parent_key: DB12268.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hyperkalemia can be increased when Mibefradil is combined with Delapril.; parent_key: DB13312.", + "drugbank-id: DB01388; name: Mibefradil; description: The therapeutic efficacy of Miconazole can be increased when used in combination with Mibefradil.; parent_key: DB01110.", + "drugbank-id: DB13728; name: Halometasone; description: The therapeutic efficacy of Capsaicin can be decreased when used in combination with Halometasone.; parent_key: DB06774.", + "drugbank-id: DB01388; name: Mibefradil; description: Mibefradil may increase the arrhythmogenic activities of Niludipine.; parent_key: DB09240.", + "drugbank-id: DB00083; name: Botulinum toxin type A; description: The risk or severity of adverse effects can be increased when Pirenzepine is combined with Botulinum toxin type A.; parent_key: DB00670.", + "drugbank-id: DB01388; name: Mibefradil; description: Mibefradil may increase the arrhythmogenic activities of Agmatine.; parent_key: DB08838.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of QTc prolongation can be increased when Mibefradil is combined with Garenoxacin.; parent_key: DB06160.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hyperkalemia can be increased when Ramipril is combined with Mibefradil.; parent_key: DB00178.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hypoglycemia can be increased when Mibefradil is combined with Insulin glargine.; parent_key: DB00047.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hypotension can be increased when Periciazine is combined with Mibefradil.; parent_key: DB01608.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hypoglycemia can be increased when Mibefradil is combined with Pramlintide.; parent_key: DB01278.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of 8-chlorotheophylline can be decreased when combined with Mibefradil.; parent_key: DB14132.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Chloroquine can be decreased when combined with Mibefradil.; parent_key: DB00608.", + "drugbank-id: DB01401; name: Choline magnesium trisalicylate; description: Choline magnesium trisalicylate may decrease the excretion rate of Salmon calcitonin which could result in a higher serum level.; parent_key: DB00017.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Zileuton can be decreased when combined with Mibefradil.; parent_key: DB00744.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Cyclobenzaprine can be decreased when combined with Mibefradil.; parent_key: DB00924.", + "drugbank-id: DB01388; name: Mibefradil; description: Isradipine may increase the arrhythmogenic activities of Mibefradil.; parent_key: DB00270.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Mibefradil can be increased when combined with Secobarbital.; parent_key: DB00418.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of QTc prolongation can be increased when Mibefradil is combined with Entinostat.; parent_key: DB11841.", + "drugbank-id: DB01388; name: Mibefradil; description: Metolazone may increase the hypotensive activities of Mibefradil.; parent_key: DB00524.", + "drugbank-id: DB00593; name: Ethosuximide; description: The risk or severity of adverse effects can be increased when Ethosuximide is combined with Brexpiprazole.; parent_key: DB09128.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Mibefradil can be decreased when combined with Siponimod.; parent_key: DB12371.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Phenprocoumon can be decreased when combined with Mibefradil.; parent_key: DB00946.", + "drugbank-id: DB01388; name: Mibefradil; description: Bencyclane may increase the arrhythmogenic activities of Mibefradil.; parent_key: DB13488.", + "drugbank-id: DB01388; name: Mibefradil; description: Mibefradil may increase the arrhythmogenic activities of Fosfructose.; parent_key: DB13863.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of QTc prolongation can be increased when Mibefradil is combined with Artemether.; parent_key: DB06697.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of QTc prolongation can be increased when Mibefradil is combined with Citalopram.; parent_key: DB00215.", + "drugbank-id: DB00347; name: Trimethadione; description: Trimethadione may increase the hyperkalemic activities of Dipotassium phosphate.; parent_key: DB09414.", + "drugbank-id: DB01388; name: Mibefradil; description: The risk or severity of hypertension can be decreased when Phenylephrine is combined with Mibefradil.; parent_key: DB00388.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Midomafetamine can be decreased when combined with Mibefradil.; parent_key: DB01454.", + "drugbank-id: DB01388; name: Mibefradil; description: The metabolism of Mephenytoin can be decreased when combined with Mibefradil.; parent_key: DB00532.", + "drugbank-id: DB01388; name: Mibefradil; description: Chlorthalidone may increase the hypotensive activities of Mibefradil.; parent_key: DB00310.", + "drugbank-id: DB01388; name: Mibefradil; description: The therapeutic efficacy of Carboxymethylcellulose can be decreased when used in combination with Mibefradil.; parent_key: DB11059." + ] + }, + { + "example_idx": 61, + "anchor_id": 5810649758504819269, + "positive_id": 10928055148197399327, + "join_paths": [ + [ + 0, + 41, + 0.21484375 + ], + [ + 0, + 10, + 0.1884765625 + ], + [ + 3, + 41, + 0.1884765625 + ], + [ + 0, + 13, + 0.1865234375 + ], + [ + 0, + 20, + 0.18359375 + ] + ], + "rows": [ + "PURPOSE: The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients.", + "PATIENTS AND METHODS: In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999.", + "Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions.", + "RESULTS: HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity.", + "TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions.", + "We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04).", + "This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17).", + "CONCLUSION: TOP2A amplification-and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.", + "Antigens, Neoplasm\nAntineoplastic Combined Chemotherapy Protocols\nBiomarkers, Tumor\nBreast Neoplasms\nChemotherapy, Adjuvant\nCyclophosphamide\nDNA Topoisomerases, Type II\nDNA-Binding Proteins\nEpirubicin\nFemale\nFluorouracil\nGene Amplification\nGene Deletion\nHumans\nIn Situ Hybridization, Fluorescence\nIsoenzymes\nMethotrexate\nPoly-ADP-Ribose Binding Proteins\nPredictive Value of Tests\nPremenopause\nReceptor, ErbB-2\nRetrospective Studies\nStereoisomerism\nTreatment Outcome" + ], + "sentences": [ + "name: Fluorac; ingredients: Diclofenac + Fluorouracil; parent_key: DB00544.", + "name: Cytoxan Tab 25mg; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Cytoxan Pws for Inj 2000mg/vial; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Pharmorubicin Rdf; ingredients: Epirubicin; parent_key: DB00445.", + "name: Pharmorubicin PFS; ingredients: Epirubicin; parent_key: DB00445.", + "name: Fluorac; ingredients: Diclofenac + Fluorouracil; parent_key: DB00586.", + "name: Procytox Vial 1000mg; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Cytoxan Tab 50mg; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Pneumovax 23; ingredients: Streptococcus pneumoniae type 1 capsular polysaccharide antigen + Streptococcus pneumoniae type 10a capsular polysaccharide antigen + Streptococcus pneumoniae type 11a capsular polysaccharide antigen + Streptococcus pneumoniae type 12f capsular polysaccharide antigen + Streptococcus pneumoniae type 14 capsular polysaccharide antigen + Streptococcus pneumoniae type 15b capsular polysaccharide antigen + Streptococcus pneumoniae type 17f capsular polysaccharide antigen + Streptococcus pneumoniae type 18c capsular polysaccharide antigen + Streptococcus pneumoniae type 19a capsular polysaccharide antigen + Streptococcus pneumoniae type 19f capsular polysaccharide antigen + Streptococcus pneumoniae type 2 capsular polysaccharide antigen + Streptococcus pneumoniae type 20 capsular polysaccharide antigen + Streptococcus pneumoniae type 22f capsular polysaccharide antigen + Streptococcus pneumoniae type 23f capsular polysaccharide antigen + Streptococcus pneumoniae type 3 capsular polysaccharide antigen + Streptococcus pneumoniae type 33f capsular polysaccharide antigen + Streptococcus pneumoniae type 4 capsular polysaccharide antigen + Streptococcus pneumoniae type 5 capsular polysaccharide antigen + Streptococcus pneumoniae type 6b capsular polysaccharide antigen + Streptococcus pneumoniae type 7f capsular polysaccharide antigen + Streptococcus pneumoniae type 8 capsular polysaccharide antigen + Streptococcus pneumoniae type 9n capsular polysaccharide antigen + Streptococcus pneumoniae type 9v capsular polysaccharide antigen; parent_key: DB10339.", + "name: Menomune-A/c/y/w-135; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13889.", + "name: Epirubicin Hydrochloride Injection; ingredients: Epirubicin; parent_key: DB00445.", + "name: Cytoxan; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Fluorouracil Injection; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Epirubicin Hydrochloride for Injection; ingredients: Epirubicin; parent_key: DB00445.", + "name: Carac; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Adrucil Inj 50mg/ml; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Verrunex; ingredients: Fluorouracil + Salicylic acid; parent_key: DB00544.", + "name: Procytox for Injection 2000mg Pws IV; ingredients: Cyclophosphamide + Sodium chloride; parent_key: DB00531.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14196.", + "name: Cyclophosphamide; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Epirubicin hydrochloride; ingredients: Epirubicin; parent_key: DB00445.", + "name: Fluvirin; ingredients: Influenza A virus A/Christchurch/16/2010 NIB-74 (H1N1) antigen (propiolactone inactivated) + Influenza A virus A/Switzerland/9715293/2013 NIB-88 (H3N2) antigen (propiolactone inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (propiolactone inactivated); parent_key: DB10781.", + "name: Tolak; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Procytox Tab 25mg; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Procytox Tab 50mg; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Luvira; ingredients: (12R)-12-hydroxyeicosapentaenoic acid + Doconexent + Omega-3 fatty acids; parent_key: DB03756.", + "name: Adrucil; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Procytox Tablets 50mg; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Procytox; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Procytox Vial 200mg; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Fluarix 2015/2016; ingredients: Influenza A virus A/Christchurch/16/2010 NIB-74XP (H1N1) antigen (formaldehyde inactivated) + Influenza A virus A/Switzerland/9715293/2013 NIB-88 (H3N2) antigen (formaldehyde inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (formaldehyde inactivated); parent_key: DB10996.", + "name: Epirubicin Hydrochloride; ingredients: Epirubicin; parent_key: DB00445.", + "name: Efudex; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Gardasil 9; ingredients: Human papillomavirus type 11 L1 capsid protein antigen + Human papillomavirus type 16 L1 capsid protein antigen + Human papillomavirus type 18 L1 capsid protein antigen + Human papillomavirus type 31 L1 capsid protein antigen + Human papillomavirus type 33 L1 capsid protein antigen + Human papillomavirus type 45 L1 capsid protein antigen + Human papillomavirus type 52 L1 capsid protein antigen + Human papillomavirus type 58 L1 capsid protein antigen + Human papillomavirus type 6 L1 capsid protein antigen; parent_key: DB10302.", + "name: ISA KNOX X2D2 WRINKLE Serum; ingredients: Methoxy PEG-12 retinamide; parent_key: DB14142.", + "name: Procytox Pws 500mg; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Botox; ingredients: Botulinum toxin type A; parent_key: DB00083.", + "name: Fluorouracil; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Procytox for Injection 2000mg Pws IV; ingredients: Cyclophosphamide + Sodium chloride; parent_key: DB09153.", + "name: Fluorouracil Injection USP; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Fluoroplex; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Epirubicin for Injection; ingredients: Epirubicin; parent_key: DB00445.", + "name: Ellence; ingredients: Epirubicin; parent_key: DB00445.", + "name: PMS-epirubicin; ingredients: Epirubicin; parent_key: DB00445.", + "name: Fluoroplex Cream 1%; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Medical Provider Single Use EZ Flu Shot Fluvirin 2015-2016; ingredients: Influenza A virus A/Christchurch/16/2010 NIB-74 (H1N1) antigen (propiolactone inactivated) + Influenza A virus A/Switzerland/9715293/2013 NIB-88 (H3N2) antigen (propiolactone inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (propiolactone inactivated); parent_key: DB10602.", + "name: Pharmorubicin Rdf Inj 50mg/vial; ingredients: Epirubicin; parent_key: DB00445.", + "name: Cytoxan Pws for Inj 1000mg/vial; ingredients: Cyclophosphamide; parent_key: DB00531.", + "name: Fluorouracil Inj 50mg/ml; ingredients: Fluorouracil; parent_key: DB00544.", + "name: Fluorouracil Cream; ingredients: Fluorouracil; parent_key: DB00544." + ] + }, + { + "example_idx": 62, + "anchor_id": 11206377144591618968, + "positive_id": 8452687978186640316, + "join_paths": [ + [ + 7, + 6, + 0.27734375 + ], + [ + 4, + 6, + 0.2578125 + ], + [ + 4, + 26, + 0.2412109375 + ], + [ + 4, + 40, + 0.2412109375 + ], + [ + 4, + 8, + 0.240234375 + ] + ], + "rows": [ + "The effects of association of cholinergic precursors choline or choline alphoscerate with the cholinesterase inhibitor rivastigmine on acetylcholine levels and [(3)H]hemicholinium-3 binding were assessed in rat frontal cortex, hippocampus and striatum.", + "Acetylcholine immunoreactivity was also evaluated in cerebrocortical cholinergic fibers by immunohistochemistry.", + "Choline alphoscerate or rivastigmine, but not choline increased acetylcholine levels as well as [(3)H]hemicholinium-3 binding used as a marker of high affinity cholinergic transporter.", + "The association of choline alphoscerate with rivastigmine dose-dependently increased both acetylcholine levels and [(3)H]hemicholinium-3 binding.", + "Rivastigmine alone or in association with either choline or choline alphoscerate decreased acetylcholinesterase (AChE), whereas choline or choline alphoscerate alone did not affect AChE activity.", + "Choline alphoscerate or rivastigmine alone or in association, but not choline increased acetylcholine immunoreactivity in nerve fibers supplying cerebral cortex.", + "These data suggest that combination of a suitable precursor of brain acetylcholine such as choline alphoscerate and of a cholinesterase inhibitor may represent an association worthwhile of being further investigated as a cholinergic replacement therapy in pathologies characterized by altered cholinergic neurotransmission.", + "Acetylcholine\nAnimals\nBrain\nBrain Chemistry\nCholinesterase Inhibitors\nGlycerylphosphorylcholine\nMale\nPhenylcarbamates\nRats\nRats, Wistar\nRivastigmine\nSignal Transduction" + ], + "sentences": [ + "id: BE0000240; name: Plasminogen activator inhibitor 1; organism: Humans; known_action: unknown; position: 4; parent_key: DB00031.", + "id: BE0000615; name: Choline-phosphate cytidylyltransferase A; organism: Humans; known_action: unknown; position: 3; parent_key: DB14006.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 2; parent_key: DB00733.", + "id: BE0009058; name: Insulin-like growth factor-binding protein complex acid labile subunit; organism: Humans; known_action: unknown; position: 84; parent_key: DB01593.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; position: 1; parent_key: DB02845.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB00944.", + "id: BE0000426; name: Acetylcholinesterase; organism: Humans; known_action: unknown; position: 5; parent_key: DB00863.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB03814.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 2; parent_key: DB00677.", + "id: BE0003438; name: Alpha-7 nicotinic cholinergic receptor subunit; organism: Humans; known_action: unknown; position: 3; parent_key: DB01043.", + "id: BE0000494; name: Choline-phosphate cytidylyltransferase B; organism: Humans; known_action: unknown; parent_key: DB00122.", + "id: BE0000212; name: High affinity cationic amino acid transporter 1; organism: Humans; known_action: unknown; parent_key: DB00125.", + "id: BE0003438; name: Alpha-7 nicotinic cholinergic receptor subunit; organism: Humans; known_action: unknown; parent_key: DB06090.", + "id: BE0003438; name: Alpha-7 nicotinic cholinergic receptor subunit; organism: Humans; known_action: yes; position: 2; parent_key: DB00202.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB06204.", + "id: BE0000178; name: Monocarboxylate transporter 8; organism: Humans; known_action: unknown; parent_key: DB00119.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB03822.", + "id: BE0000212; name: High affinity cationic amino acid transporter 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00129.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 2; parent_key: DB13581.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB03672.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB00122.", + "id: BE0004643; name: Penicillin-binding protein 3; organism: Streptococcus pneumoniae; known_action: yes; position: 5; parent_key: DB00607.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 1; parent_key: DB00382.", + "id: BE0009912; name: Peptidoglycan precursors; known_action: yes; position: 6; parent_key: DB04911.", + "id: BE0003438; name: Alpha-7 nicotinic cholinergic receptor subunit; organism: Humans; known_action: unknown; position: 1; parent_key: DB01520.", + "id: BE0000212; name: High affinity cationic amino acid transporter 1; organism: Humans; known_action: unknown; parent_key: DB00123.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 15; parent_key: DB01221.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; parent_key: DB01057.", + "id: BE0004060; name: Multi-sensor signal transduction histidine kinase; organism: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099); known_action: unknown; position: 2; parent_key: DB02731.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; parent_key: DB00989.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; position: 4; parent_key: DB00674.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; position: 4; parent_key: DB01226.", + "id: BE0000901; name: Low affinity immunoglobulin gamma Fc region receptor III-B; organism: Humans; known_action: unknown; parent_key: DB00110.", + "id: BE0000615; name: Choline-phosphate cytidylyltransferase A; organism: Humans; known_action: unknown; parent_key: DB00122.", + "id: BE0003438; name: Alpha-7 nicotinic cholinergic receptor subunit; organism: Humans; known_action: unknown; position: 7; parent_key: DB00193.", + "id: BE0003624; name: Penicillin-binding protein 2B; organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6); known_action: yes; position: 3; parent_key: DB00607.", + "id: BE0000519; name: Choline O-acetyltransferase; organism: Humans; known_action: unknown; position: 27; parent_key: DB00184.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB04250.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 1; parent_key: DB00545.", + "id: BE0003438; name: Alpha-7 nicotinic cholinergic receptor subunit; organism: Humans; known_action: yes; position: 14; parent_key: DB01221.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 1; parent_key: DB01010.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; position: 4; parent_key: DB00449.", + "id: BE0009708; name: Group A nerve fibers; organism: Rat; known_action: unknown; position: 2; parent_key: DB01438.", + "id: BE0002100; name: Low affinity immunoglobulin gamma Fc region receptor II-c; organism: Humans; known_action: unknown; position: 5; parent_key: DB00005.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB03568.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; parent_key: DB00772.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: yes; parent_key: DB00941.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; parent_key: DB02811.", + "id: BE0002180; name: Cholinesterase; organism: Humans; known_action: unknown; position: 4; parent_key: DB00843.", + "id: BE0000494; name: Choline-phosphate cytidylyltransferase B; organism: Humans; known_action: unknown; position: 1; parent_key: DB14006." + ] + }, + { + "example_idx": 63, + "anchor_id": 16714291366094709500, + "positive_id": 9267972536695414481, + "join_paths": [ + [ + 9, + 25, + 0.306640625 + ], + [ + 9, + 32, + 0.306640625 + ], + [ + 9, + 42, + 0.306640625 + ], + [ + 9, + 2, + 0.3046875 + ], + [ + 9, + 8, + 0.3046875 + ] + ], + "rows": [ + "Perindopril is a third-generation ACE inhibitor that is characterised as a small, lipophilic molecule with a therapeutically active carboxyl side group.", + "These and other features combine to make this a unique member of a very well-established class of drugs that have proven efficacy in a wide range of cardiovascular diseases.", + "The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) demonstrated benefit in the secondary prevention of patients with stroke, whereas the Perindopril and Remodelling in Elderly with Acute Myocardial Infarction (PREAMI) trial supports extended routine use after myocardial infarction.", + "The most recent evidence from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) show that perindopril is able to improve the prognosis of patients with a relatively low global cardiovascular risk, denoted either by the presence of stable coronary artery disease or of essential hypertension in conjunction with at least three other risk factors.", + "The fact that major relative risk reductions have been reported for these two studies is matched by the significance of the findings to modern clinical practice.", + "Both studies were conducted in the context of advance concomitant care that is typically better in clinical trials than in routine practice.", + "In particular, the benefits observed were seen to be of a similar magnitude, and also independent of those resulting from statin therapy.", + "Of particular interest is the likely complimentary action of these treatment strategies with regard to the stabilisation of atheromatous plaques.", + "Perindopril is a well-established drug, the full value of which is only now becoming fully apparent.", + "Angiotensin-Converting Enzyme Inhibitors\nAnimals\nAntihypertensive Agents\nCardiovascular Diseases\nHumans\nPerindopril" + ], + "sentences": [ + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00790.", + "id: BE0000090; name: Potassium voltage-gated channel subfamily H member 2; organism: Humans; known_action: unknown; position: 8; parent_key: DB00280.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00492.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: unknown; parent_key: DB03740.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB01180.", + "id: BE0003623; name: Cation-independent mannose-6-phosphate receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB01277.", + "id: BE0000982; name: Angiotensin-converting enzyme 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB15643.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: unknown; parent_key: DB02032.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB01340.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB07947.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00178.", + "id: BE0002098; name: Low affinity immunoglobulin gamma Fc region receptor II-a; organism: Humans; known_action: yes; position: 3; parent_key: DB00028.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB13166.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB15565.", + "id: BE0000982; name: Angiotensin-converting enzyme 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB01611.", + "id: BE0000867; name: Cocaine- and amphetamine-regulated transcript protein; organism: Humans; known_action: yes; position: 3; parent_key: DB00182.", + "id: BE0001024; name: Troponin C, slow skeletal and cardiac muscles; organism: Humans; known_action: unknown; position: 13; parent_key: DB01023.", + "id: BE0003623; name: Cation-independent mannose-6-phosphate receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB14751.", + "id: BE0000450; name: Leucine carboxyl methyltransferase 1; organism: Humans; known_action: unknown; parent_key: DB00149.", + "id: BE0001105; name: Major prion protein; organism: Humans; known_action: unknown; position: 7; parent_key: DB00759.", + "id: BE0003793; name: Endothelin-converting enzyme 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB07171.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00531.", + "id: BE0000090; name: Potassium voltage-gated channel subfamily H member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB01195.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB09477.", + "id: BE0000967; name: Tissue factor pathway inhibitor; organism: Humans; known_action: unknown; parent_key: DB00036.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: unknown; position: 3; parent_key: DB08836.", + "id: BE0001085; name: Intercellular adhesion molecule 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB00108.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB01197.", + "id: BE0003428; name: High mobility group protein B1; organism: Humans; known_action: unknown; parent_key: DB05869.", + "id: BE0000982; name: Angiotensin-converting enzyme 2; organism: Humans; known_action: unknown; position: 11; parent_key: DB00608.", + "id: BE0003623; name: Cation-independent mannose-6-phosphate receptor; organism: Humans; known_action: unknown; parent_key: DB02900.", + "id: BE0003502; name: Heat-stable enterotoxin receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB08890.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00691.", + "id: BE0000982; name: Angiotensin-converting enzyme 2; organism: Humans; known_action: unknown; parent_key: DB05203.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00519.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00584.", + "id: BE0009040; name: Ubiquitin carboxyl-terminal hydrolase 14; organism: Humans; known_action: unknown; position: 38; parent_key: DB12695.", + "id: BE0004144; name: Calpain small subunit 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB02570.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00542.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: unknown; position: 1; parent_key: DB00616.", + "id: BE0002446; name: Epithelial cell adhesion molecule; organism: Humans; known_action: unknown; parent_key: DB05319.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00722.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00881.", + "id: BE0001085; name: Intercellular adhesion molecule 1; organism: Humans; known_action: unknown; position: 6; parent_key: DB12598.", + "id: BE0002565; name: B12-independent glycerol dehydratase; organism: Clostridium butyricum; known_action: unknown; parent_key: DB01839.", + "id: BE0003623; name: Cation-independent mannose-6-phosphate receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB13173.", + "id: BE0001085; name: Intercellular adhesion molecule 1; organism: Humans; known_action: yes; position: 2; parent_key: DB08818.", + "id: BE0000613; name: Leucine carboxyl methyltransferase 2; organism: Humans; known_action: unknown; parent_key: DB00149.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB01348.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: unknown; position: 1; parent_key: DB00886." + ] + }, + { + "example_idx": 64, + "anchor_id": 10559862199235554, + "positive_id": 7477644494429113908, + "join_paths": [ + [ + 0, + 5, + 0.259765625 + ], + [ + 0, + 39, + 0.25390625 + ], + [ + 0, + 49, + 0.25390625 + ], + [ + 0, + 48, + 0.2451171875 + ], + [ + 0, + 1, + 0.2294921875 + ] + ], + "rows": [ + "Fentanyl is a highly potent and clinically widely used narcotic analgesic.", + "The synthesis of its analogs remains a challenge in the attempt to develop highly selective mu-opioid receptor agonists with specific pharmacological properties.", + "In this paper, the use of flexible molecular docking in a study of the formation of complexes between a series of active fentanyl analogs and the mu-opioid receptor is described.", + "The optimal position and orientation of fourteen fentanyl analogs in the binding pocket of the mu-receptor were determined.", + "The major receptor amino acids and the ligand functional groups participating in the complex formation were identified.", + "Stereochemical effects on the potency and binding are explained.", + "The proposed model of ligand-receptor binding is in agreement with point mutation experiments explaining the role of the amino acids: Asp147, Tyr148, Asn230, His297, Trp318, His319, Cys321, and Tyr326 in the complex formation.", + "In addition, the following amino acids were identified as being important for ligand binding or receptor activation: Ile322, Gly325, Val300, Met203, Leu200, Val143, and Ile144.", + "Binding Sites\nFentanyl\nHydrophobic and Hydrophilic Interactions\nHydroxylation\nMethylation\nModels, Molecular\nProtein Structure, Tertiary\nReceptors, Opioid, mu\nStructure-Activity Relationship" + ], + "sentences": [ + "name: Duragesic 75; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl System; ingredients: Fentanyl; parent_key: DB00813.", + "name: Sublimaze Inj 50mcg/ml; ingredients: Fentanyl; parent_key: DB00813.", + "name: Ran-fentanyl Transdermal System; ingredients: Fentanyl; parent_key: DB00813.", + "name: Duragesic; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl; ingredients: Fentanyl; parent_key: DB00813.", + "name: Sublimaze; ingredients: Fentanyl; parent_key: DB00813.", + "name: Abstral fentanyl; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Citrate Injection USP; ingredients: Fentanyl; parent_key: DB00813.", + "name: Subsys; ingredients: Fentanyl; parent_key: DB00813.", + "name: Tricare Prenatal Compleat; ingredients: Ascorbic acid + Calcium carbonate + Cholecalciferol + Cupric sulfate + Cyanocobalamin + DL-alpha tocopheryl acetate + Doconexent + Ferrous fumarate + Folic acid + Gondoic acid + Nicotinamide + Omega-3 fatty acids + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB06778.", + "name: Fentanyl Citrate Injection USP 50mcg/ml; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Transdermal System 75; ingredients: Fentanyl; parent_key: DB00813.", + "name: Yellow Jacket hymenoptera venom Venomil Maintenance; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11030.", + "name: Duragesic 50; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Citrate Injection Sdz; ingredients: Fentanyl; parent_key: DB00813.", + "name: Duragesic 100; ingredients: Fentanyl; parent_key: DB00813.", + "name: Venelex; ingredients: Balsam of Peru + Castor oil; parent_key: DB11482.", + "name: Taron-C DHA; ingredients: Ascorbic acid + Biotin + Cupric sulfate + Cyanocobalamin + Ferrous fumarate + Folic acid + Iron + Magnesium sulfate + Niacin + Omega-3 fatty acids + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Zinc sulfate, unspecified form; parent_key: DB00152.", + "name: Fentora; ingredients: Fentanyl; parent_key: DB00813.", + "name: Duragesic 25; ingredients: Fentanyl; parent_key: DB00813.", + "name: Mylan-fentanyl Matrix Patch; ingredients: Fentanyl; parent_key: DB00813.", + "name: Ionsys; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Buccal; ingredients: Fentanyl; parent_key: DB00813.", + "name: Abstral; ingredients: Fentanyl; parent_key: DB00813.", + "name: Instanyl; ingredients: Fentanyl; parent_key: DB00813.", + "name: Teva-fentanyl; ingredients: Fentanyl; parent_key: DB00813.", + "name: DURAGESIC (fentanyl system); ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Transdermal System; ingredients: Fentanyl; parent_key: DB00813.", + "name: PMS-fentanyl Mtx; ingredients: Fentanyl; parent_key: DB00813.", + "name: Ran-fentanyl Matrix Patch; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl transdermal system; ingredients: Fentanyl; parent_key: DB00813.", + "name: Effentora; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Transdermal; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Citrate Injection U.S.P.-liq IV Im Epd; ingredients: Fentanyl; parent_key: DB00813.", + "name: Transmucosal Fentanyl Citrate; ingredients: Fentanyl; parent_key: DB00813.", + "name: Actiq; ingredients: Fentanyl; parent_key: DB00813.", + "name: Duragesic 12; ingredients: Fentanyl; parent_key: DB00813.", + "name: Cavan Alpha; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Folic acid + Iodine + Iron + Magnesium oxide + Nicotinamide + Omega-3 fatty acids + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB00169.", + "name: Fentanyl Citrate; ingredients: Fentanyl; parent_key: DB00813.", + "name: Mixed Vespid Hymenoptera Venom Multidose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Hymenoptera Venom Diagnostic; ingredients: Apis mellifera venom + Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Polistes fuscatus venom protein + Vespula maculifrons venom protein; parent_key: DB10957.", + "name: Cervarix; ingredients: Human papillomavirus type 16 L1 capsid protein residues 2-471 antigen + Human papillomavirus type 18 l1 capsid protein residues 2-472 antigen; parent_key: DB10994.", + "name: Duet DHA Balanced; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Choline + Cupric oxide + Cyanocobalamin + D-alpha-Tocopherol acetate + Folic acid + Iodine + Iron + Magnesium + Nicotinamide + Omega-3 fatty acids + Pyridoxine + Riboflavin + Selenic acid + Thiamine + Zinc oxide; parent_key: DB14513.", + "name: Lazanda; ingredients: Fentanyl; parent_key: DB00813.", + "name: Onsolis; ingredients: Fentanyl; parent_key: DB00813.", + "name: Sandoz Fentanyl Patch; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Transdermal System 25; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl Patch; ingredients: Fentanyl; parent_key: DB00813.", + "name: Fentanyl - NOVAPLUS; ingredients: Fentanyl; parent_key: DB00813." + ] + }, + { + "example_idx": 65, + "anchor_id": 499704009332173404, + "positive_id": 8184826376814516359, + "join_paths": [ + [ + 13, + 6, + 0.2138671875 + ], + [ + 12, + 39, + 0.1845703125 + ], + [ + 12, + 35, + 0.1689453125 + ], + [ + 12, + 21, + 0.16796875 + ], + [ + 12, + 30, + 0.16796875 + ] + ], + "rows": [ + "Ivermectin is a potent antiparasitic drug from macrocyclic lactone (ML) family, which interacts with the ABC multidrug transporter P-glycoprotein (Pgp).", + "We studied the interactions of ivermectin with the multidrug resistance proteins (MRPs) by combining cellular and subcellular approaches.", + "The inhibition by ivermectin of substrate transport was measured in A549 cells (calcein or 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, BCECF) and in HL60-MRP1 (calcein).", + "Ivermectin induced calcein and BCECF retention in A549 cells (IC(50) at 1 and 2.5microM, respectively) and inhibited calcein efflux in HL60-MRP1 (IC(50)=3.8microM).", + "The action of ivermectin on the transporters ATPase activity was followed on membranes from Sf9 cells overexpressing human Pgp, MRP1, 2 or 3.", + "Ivermectin inhibited the Pgp, MRP1, 2 and 3 ATPase activities after stimulation by their respective activators.", + "Ivermectin showed a rather good affinity for MRPs, mainly MRP1, in the micromolar range, although it was lower than that for Pgp.", + "The transport of BODIPY-ivermectin was followed in cells overexpressing selectively Pgp or MRP1.", + "In both cell lines, inhibition of the transporter activity induced intracellular retention of BODIPY-ivermectin.", + "Our data revealed the specific interaction of ivermectin with MRP proteins, and its transport by MRP1.", + "Although Pgp has been considered until now as the sole active transporter for this drug, the MRPs should be taken into account for the transport of ivermectin across cell membrane, modulating its disposition in addition to Pgp.", + "This could be of importance for optimizing clinical efficacy of ML-based antiparasitic treatments.", + "This offers fair perspectives for the use of ivermectin or non-toxic derivatives as multidrug resistance-reversing agents.", + "ATP Binding Cassette Transporter, Subfamily B\nAdenosine Triphosphatases\nAnimals\nBiological Transport\nCell Line\nCell Membrane\nGene Expression Regulation\nHumans\nIvermectin\nMolecular Structure\nSpodoptera\nSubstrate Specificity\nSwine" + ], + "sentences": [ + "id: BE0003640; name: Multidrug resistance-associated protein 6; organism: Humans; known_action: unknown; position: 8; parent_key: DB01032.", + "id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: no; position: 11; parent_key: DB09130.", + "id: BE0001042; name: Solute carrier organic anion transporter family member 2B1; organism: Humans; known_action: unknown; position: 14; parent_key: DB00641.", + "id: BE0001188; name: Multidrug resistance-associated protein 4; organism: Humans; known_action: unknown; position: 11; parent_key: DB00563.", + "id: BE0001188; name: Multidrug resistance-associated protein 4; organism: Humans; known_action: unknown; position: 1; parent_key: DB02527.", + "id: BE0003651; name: Multidrug resistance-associated protein 7; organism: Humans; known_action: unknown; position: 17; parent_key: DB13953.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB00394.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 10; parent_key: DB00345.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00694.", + "id: BE0003666; name: Copper-transporting ATPase 1; organism: Humans; known_action: no; position: 10; parent_key: DB09130.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00365.", + "id: BE0004707; name: Solute carrier family 2, facilitated glucose transporter member 3; organism: Humans; known_action: no; position: 5; parent_key: DB01914.", + "id: BE0003646; name: Solute carrier family 22 member 7; organism: Humans; known_action: unknown; position: 8; parent_key: DB00495.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB01232.", + "id: BE0001188; name: Multidrug resistance-associated protein 4; organism: Humans; known_action: unknown; position: 21; parent_key: DB01708.", + "id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: unknown; position: 14; parent_key: DB00526.", + "id: BE0003639; name: Multidrug resistance-associated protein 5; organism: Humans; known_action: unknown; position: 2; parent_key: DB02527.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 6; parent_key: DB00396.", + "id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB00515.", + "id: BE0000276; name: Solute carrier family 12 member 7; organism: Humans; known_action: unknown; position: 5; parent_key: DB00761.", + "id: BE0003666; name: Copper-transporting ATPase 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB00958.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 20; parent_key: DB09213.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB11986.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB04216.", + "id: BE0003639; name: Multidrug resistance-associated protein 5; organism: Humans; known_action: unknown; position: 1; parent_key: DB00770.", + "id: BE0001188; name: Multidrug resistance-associated protein 4; organism: Humans; known_action: unknown; position: 3; parent_key: DB00203.", + "id: BE0009848; name: Human vesicular glutamate transporters; organism: Humans; known_action: unknown; position: 6; parent_key: DB00814.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 9; parent_key: DB00603.", + "id: BE0009791; name: ABC multidrug transporter MDR2; organism: Trichophyton interdigitale (strain MR816); known_action: unknown; position: 5; parent_key: DB00857.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00997.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB08881.", + "id: BE0003651; name: Multidrug resistance-associated protein 7; organism: Humans; known_action: unknown; position: 19; parent_key: DB00661.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB02375.", + "id: BE0000508; name: Cellular retinoic acid-binding protein 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB00755.", + "id: BE0000782; name: Cellular retinoic acid-binding protein 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00755.", + "id: BE0003640; name: Multidrug resistance-associated protein 6; organism: Humans; known_action: unknown; position: 9; parent_key: DB01138.", + "id: BE0001188; name: Multidrug resistance-associated protein 4; organism: Humans; known_action: unknown; position: 1; parent_key: DB00482.", + "id: BE0003651; name: Multidrug resistance-associated protein 7; organism: Humans; known_action: unknown; position: 3; parent_key: DB00694.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB00693.", + "id: BE0003641; name: Multidrug resistance protein 3; organism: Humans; known_action: unknown; position: 4; parent_key: DB06207.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00445.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 4; parent_key: DB00541.", + "id: BE0003640; name: Multidrug resistance-associated protein 6; organism: Humans; known_action: unknown; position: 4; parent_key: DB00570.", + "id: BE0001188; name: Multidrug resistance-associated protein 4; organism: Humans; known_action: unknown; position: 9; parent_key: DB02659.", + "id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB00958.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 11; parent_key: DB01016.", + "id: BE0001134; name: Solute carrier family 15 member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00577.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 9; parent_key: DB01232.", + "id: BE0003651; name: Multidrug resistance-associated protein 7; organism: Humans; known_action: unknown; position: 2; parent_key: DB00441.", + "id: BE0003651; name: Multidrug resistance-associated protein 7; organism: Humans; known_action: unknown; position: 2; parent_key: DB01248." + ] + }, + { + "example_idx": 66, + "anchor_id": 3741371861853682319, + "positive_id": 9022262973277840794, + "join_paths": [ + [ + 1, + 0, + 0.2001953125 + ], + [ + 1, + 26, + 0.197265625 + ], + [ + 1, + 20, + 0.1962890625 + ], + [ + 1, + 21, + 0.1962890625 + ], + [ + 1, + 25, + 0.1953125 + ] + ], + "rows": [ + "CONTEXT: Side effects of mitotane (o,p'-DDD) have suggested estrogenic effects.", + "OBJECTIVE: The objective of the study was to explore o,p'-DDD potential estrogenic effect on SHBG and corticosteroid-binding globulin (CBG).", + "DESIGN: Human hepatoma cell lines (HepG2), lacking estrogen receptor (ER)-alpha, and Hep89, stably transfected by ERalpha, were used.", + "SETTING: The study was conducted at an academic research laboratory and medical center.", + "PATIENTS AND OTHER PARTICIPANTS: The study included 10 male patients with recurrent adrenal carcinoma, receiving mitotane (4-6.5 g daily) for more than 6 months.", + "MAIN OUTCOME MEASURES: The main outcome measures were SHBG/CBG mRNA levels measured by real-time PCR, culture medium SHBG/CBG concentrations measured by specific immunoassays, and transient transfection experiments with human SHBG proximal promoter reporter constructs.", + "RESULTS: Increased serum SHBG and CBG concentrations, which exceeded normal male limits, were observed in most mitotane-treated patients.", + "In the HepG2 cell line, 17beta-estradiol (E2) or o,p'-DDD treatment had no effect on mRNA or SHBG/CBG concentrations.", + "In contrast, in the Hep89 cell line, E2 increased concentrations of SHBG (r = 0.44, P < 0.0001) and CBG (r = 0.585, P < 0.0001) secreted into culture media in a dose-dependent manner.", + "o,p'-DDD significantly increased SHBG (150% vs. control, P < 0.05) and CBG (184% vs. control, P < 0.05) production by Hep89 cells, at a concentration of 2 x 10(-5) m. Transient transfection experiments in Hep89 cells showed that E2 or o,p'-DDD treatment did not increase the transcriptional activity of the minimal proximal promoter of human SHBG gene.", + "CONCLUSIONS: Mitotane increased SHBG/CBG gene expression and liver production by mechanisms requiring the presence of ERalpha.", + "Adrenal Gland Neoplasms\nAntineoplastic Agents, Hormonal\nEstradiol\nEstrogen Receptor alpha\nHumans\nLiver\nMale\nMitotane\nPromoter Regions, Genetic\nRNA, Messenger\nSex Hormone-Binding Globulin\nTranscortin\nTranscription, Genetic\nTumor Cells, Cultured" + ], + "sentences": [ + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 13; parent_key: DB14544.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 4; parent_key: DB01364.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 2; parent_key: DB00394.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 5; parent_key: DB00304.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 2; parent_key: DB09236.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00588.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 2; parent_key: DB00591.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 23; parent_key: DB00286.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: yes; position: 2; parent_key: DB01410.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB05688.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: no; position: 5; parent_key: DB13943.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 13; parent_key: DB14540.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 8; parent_key: DB08906.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 1; parent_key: DB00753.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 6; parent_key: DB00635.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00253.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 6; parent_key: DB00687.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB01047.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 5; parent_key: DB14669.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 3; parent_key: DB00294.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 1; parent_key: DB15566.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 11; parent_key: DB14542.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00240.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: no; position: 4; parent_key: DB09124.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 2; parent_key: DB00846.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 11; parent_key: DB14538.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 11; parent_key: DB14541.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; parent_key: DB03926.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 13; parent_key: DB14539.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: yes; position: 2; parent_key: DB00180.", + "id: BE0000786; name: Retinaldehyde-binding protein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00162.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 5; parent_key: DB13867.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00648.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 12; parent_key: DB01222.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 13; parent_key: DB14543.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 6; parent_key: DB01013.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00663.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00324.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 2; parent_key: DB00860.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB01384.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 12; parent_key: DB00443.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 6; parent_key: DB00741.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 17; parent_key: DB14631.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00596.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; position: 2; parent_key: DB00620.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: no; position: 3; parent_key: DB09053.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: no; position: 15; parent_key: DB00321.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 11; parent_key: DB00273.", + "id: BE0000925; name: Alpha-1-acid glycoprotein 1; organism: Humans; known_action: no; position: 22; parent_key: DB01142.", + "id: BE0000209; name: Corticosteroid-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00896." + ] + }, + { + "example_idx": 67, + "anchor_id": 1088101828940402163, + "positive_id": 10146054104697668643, + "join_paths": [ + [ + 2, + 23, + 0.232421875 + ], + [ + 0, + 23, + 0.224609375 + ], + [ + 3, + 0, + 0.1904296875 + ], + [ + 12, + 23, + 0.1845703125 + ] + ], + "rows": [ + "The clinical use of monoamine oxidase inhibitors (MAOIs) has declined due to concerns about food and drug interactions and waning physician experience.", + "Evidence indicates that MAOIs are effective in depressive disorders, in particular depression with atypical features.", + "Efforts to address safety issues have led to the development of more selective and reversible MAOIs, such as moclobemide.", + "Selegiline, a selective monoamine oxidase B inhibitor, has been approved for the adjunctive treatment of Parkinson's disease at low doses.", + "At higher doses, oral selegiline is also effective in major depressive disorder (MDD) but loses its selectivity and has the potential for tyramine interactions.", + "To overcome these problems, a transdermal formulation of selegiline, the selegiline transdermal system (STS), was developed with novel pharmacokinetic and pharmacodynamic properties.", + "Compared with oral administration, transdermal selegiline leads to sustained plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain and decreasing metabolite production.", + "In addition, STS allows targeted inhibition of central nervous system monoamine A (MAO-A) and monoamine B isoenzymes with minimal effects on MAO-A in the gastrointestinal and hepatic systems, thereby reducing the risk of interactions with tyramine-rich foods (the \"cheese-reaction\").", + "Clinical trials have found 6 mg/24 hours of STS to be effective in MDD without the need for dietary restrictions.", + "The efficacy and safety profile of STS supports its use in MDD.", + "It is possible that STS may demonstrate benefit in MDD with atypical features or MDD resistant to other antidepressants.", + "However, more research is needed.", + "Clinicians should familiarize themselves with the properties and indications for the new generation of MAOIs.", + "Administration, Cutaneous\nDepressive Disorder, Major\nDrug Interactions\nHumans\nMonoamine Oxidase Inhibitors\nPhenelzine\nSelegiline\nTranylcypromine" + ], + "sentences": [ + "ref-id: L2336; title: Opicapone:once-daily adjunctive therapy for Parkinson’s disease; url: https://onlinelibrary.wiley.com/doi/pdf/10.1002/psb.1543; parent_key: DB11632.", + "ref-id: L315; title: CENTER FOR DRUG EVALUATION AND RESEARCH ; url: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209115Orig1s000MultiDisciplineR.pdf; parent_key: DB12332.", + "ref-id: L5509; title: Parkinson; url: https://www.parkinson.org/sites/default/files/attachments/Parkinsons-Disease-vs-Parkinsonisms.pdf; parent_key: DB00245.", + "ref-id: L5876; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02499146; parent_key: DB09073.", + "ref-id: L547; title: Skin care research; url: http://www.smartskincare.com/skinprotection/sunblocks/sunblock_octocylene.html; parent_key: DB09535.", + "ref-id: L4834; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02181660; parent_key: DB12141.", + "ref-id: L12666; title: Efficacy and Safety of Corticosteroids in COVID-19; url: https://clinicaltrials.gov/ct2/show/NCT04273321; parent_key: DB00959.", + "ref-id: L7240; title: FDA Approved Drug Products: Catapres Clonidine Transdermal System; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018891s028lbl.pdf; parent_key: DB00575.", + "ref-id: L8995; title: FDA Approved Drug Products: Androderm Testosterone Transdermal System; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020489s034lbl.pdf; parent_key: DB00624.", + "ref-id: L1464; title: Military trauma research; url: http://www.dtic.mil/dtic/tr/fulltext/u2/a217721.pdf; parent_key: DB09255.", + "ref-id: L1078; title: Clinical experience with tixocortol pivalate; url: http://downloads.hindawi.com/journals/cjgh/1988/819089.pdf; parent_key: DB09091.", + "ref-id: L2339; title: Clinical pharmacology review of opicapone for the treatment of Parkinson's disease; url: https://www.futuremedicine.com/doi/10.2217/nmt-2016-0022; parent_key: DB11632.", + "ref-id: L12405; title: FDA Center for Drug Evaluation and Research: Pitolisant Non-clinical Review(s); url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf; parent_key: DB11642.", + "ref-id: L1715; title: Phase I–II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer ; url: https://academic.oup.com/annonc/article/16/3/430/159840; parent_key: DB06263.", + "ref-id: L2089; title: Absorption and metabolism of oral zinc gluconate in humans in fasting state, during, and after a meal; url: https://link.springer.com/article/10.1007/BF02784604; parent_key: DB11248.", + "ref-id: L2782; title: Current Trends in Photoprotection - A New Generation of Oral Photoprotectors; url: https://www.researchgate.net/profile/Angeles_Juarranz/publication/228352216_Current_Trends_in_Photoprotection-A_New_Generation_of_Oral_Photoprotectors/links/542be3990cf277d58e8a4f3f/Current-Trends-in-Photoprotection-A-New-Generation-of-Oral-Photoprotectors.pdf; parent_key: DB11585.", + "ref-id: L1770; title: CENTER FOR DRUG EVALUATION AND RESEARCH- 20755; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020725s000PharmR.pdf; parent_key: DB00085.", + "ref-id: L10442; title: FDA Approved Drug Products: Daytrana® transdermal system; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021514s030lbl.pdf; parent_key: DB00422.", + "ref-id: L8591; title: FDA Approved Drug Products: Fenofibrate Oral Capsules; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021612s020lbl.pdf; parent_key: DB01039.", + "ref-id: L5314; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT03172208; parent_key: DB06081.", + "ref-id: L11890; title: Health Canada Product Monograph: Trimethoprim oral tablets; url: https://pdf.hres.ca/dpd_pm/00025165.PDF; parent_key: DB00440.", + "ref-id: L7988; title: FDA Approved Drug Products: Nebivolol and Valsartan Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206302s000lbl.pdf; parent_key: DB04861.", + "ref-id: L322; title: CENTER FOR DRUG EVALUATION AND RESEARCH ; url: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209531Orig1s000ClinPharmR.pdf; parent_key: DB13161.", + "ref-id: L1350; title: Monamine Oxidase Inhibitors; url: https://books.google.ca/books?id=iUi5ErxyhVYC&pg=PA191&lpg=PA191&dq=moclobemide+clearance&source=bl&ots=9-XcLmfB1Y&sig=jKPdSO_2hzyh2adnG3Ap73GqEZQ&hl=en&sa=X&ved=0ahUKEwiPxOSHgrXZAhUY5WMKHeVgCk44ChDoAQgoMAA#v=onepage&q=moclobemide%20clearance&f=false; parent_key: DB01171.", + "ref-id: L4846; title: American Society of Hematology; url: http://www.hematology.org/Thehematologist/Mini-Review/8257.aspx; parent_key: DB14724.", + "ref-id: L1867; title: National Institute for Health Research; url: http://www.io.nihr.ac.uk/wp-content/uploads/migrated/Vonicog-alfa-Feb16.pdf; parent_key: DB12872.", + "ref-id: L1770; title: CENTER FOR DRUG EVALUATION AND RESEARCH- 20755; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020725s000PharmR.pdf; parent_key: DB11074.", + "ref-id: L852; title: American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017.; url: http://hcvguidelines.org/full-report-view; parent_key: DB11574.", + "ref-id: L773; title: FDA Center for Drug Evaluation and Research: Summary Review; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022532Orig1s000SumR.pdf; parent_key: DB11256.", + "ref-id: L1136; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/results/NCT02411929?sect=Xgf0156#outcome10; parent_key: DB11827.", + "ref-id: L4835; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02456883; parent_key: DB12141.", + "ref-id: L4841; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01818492; parent_key: DB14724.", + "ref-id: L4883; title: Canadian Society of Intestinal Research; url: https://www.badgut.org/information-centre/a-z-digestive-topics/serious-toll-of-chronic-constipation-overlooked/; parent_key: DB06480.", + "ref-id: L10301; title: FDA Approved Drug Products: CombiPatch® transdermal system; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020870s023lbl.pdf; parent_key: DB00717.", + "ref-id: L1168; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/record/NCT02612298?view=results; parent_key: DB09204.", + "ref-id: L1387; title: A reversible monoamine oxidase inhibitor, toloxatone: spectrophotometric and molecular orbital studies of the interaction with flavin adenine dinucleotide (FAD); url: https://www.sciencedirect.com/science/article/pii/0223523494900965; parent_key: DB09245.", + "ref-id: L11497; title: FDA Approved Products: Climara (estradiol) transdermal system; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020375s026lbl.pdf; parent_key: DB00783.", + "ref-id: L1770; title: CENTER FOR DRUG EVALUATION AND RESEARCH- 20755; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020725s000PharmR.pdf; parent_key: DB11065.", + "ref-id: L6511; title: Ketorolac: A Reappraisal of its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use In Pain Management; url: https://link.springer.com/article/10.2165/00003495-199753010-00012; parent_key: DB00465.", + "ref-id: L1867; title: National Institute for Health Research; url: http://www.io.nihr.ac.uk/wp-content/uploads/migrated/Vonicog-alfa-Feb16.pdf; parent_key: DB13133.", + "ref-id: L2480; title: Molecular Targets of Aspirin and Cancer Prevention; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090734/; parent_key: DB11071.", + "ref-id: L11530; title: FDA Approved Products: Esclim (Estradiol) transdermal system; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20847lblpt.pdf; parent_key: DB00783.", + "ref-id: L1654; title: World Health Organization - Yellow fever vaccination booster not needed; url: http://www.who.int/mediacentre/news/releases/2013/yellow_fever_20130517/en/; parent_key: DB10805.", + "ref-id: L5798; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01123486; parent_key: DB00327.", + "ref-id: L1413; title: Tianeptine properties; url: http://datasheets.scbt.com/sds/aghs/en/sc-204345.pdf; parent_key: DB09289.", + "ref-id: L5476; title: WHO Pharmaceuticals: Restrictions in Use and Availability (2001; 40 pages) View the PDF document; url: http://apps.who.int/medicinedocs/en/d/Js2203e/2.50.html; parent_key: DB13253.", + "ref-id: L1676; title: Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395437/; parent_key: DB11590.", + "ref-id: L7141; title: Transdermal nitroglycerin; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020145s027lbl.pdf; parent_key: DB00727.", + "ref-id: L4811; title: FDA Approves Two New Indications for Rituxan in Patients With Non-Hodgkin's Lymphoma; url: https://www.gene.com/media/press-releases/10047/2006-09-29/fda-approves-two-new-indications-for-rit; parent_key: DB00073.", + "ref-id: L1021; title: FDA Approved Drugs: Letermovir; url: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=209939; parent_key: DB12070." + ] + }, + { + "example_idx": 68, + "anchor_id": 6321488042393930814, + "positive_id": 16579119923799706070, + "join_paths": [ + [ + 12, + 24, + 0.32421875 + ], + [ + 12, + 48, + 0.32421875 + ], + [ + 1, + 29, + 0.279296875 + ], + [ + 2, + 26, + 0.263671875 + ], + [ + 0, + 24, + 0.259765625 + ] + ], + "rows": [ + "Symptom reduction and improvement in functioning in women with postpartum major depression treated with a tricyclic antidepressant versus a serotonin reuptake inhibitor were compared.", + "The design was a double-blind, 8-week comparative trial of nortriptyline (NTP) versus sertraline (SERT) with a 16-week continuation phase.", + "Women aged 18 to 45 years with postpartum major depression and a 17-item Hamilton Rating Scale for Depression score of 18 or more were eligible.", + "Subjects were randomized to NTP or SERT and treated with a fixed-dosing strategy.", + "Of 420 women interviewed, 109 eligible women received medication, and 95 provided follow-up data.", + "The proportion of women who responded and remitted did not differ between drugs at 4, 8, or 24 weeks.", + "Times to response and remission also did not differ.", + "Psychosocial functioning improved similarly in both drug-treated groups of mothers.", + "The total side effect burden of each drug was similar, although side effect profiles differed between agents.", + "No clinical or demographic variables differentiated responders by drug.", + "Women who were responders and remitters at week 8 could be identified earlier if they were treated with SERT than with NTP.", + "Breast-fed infant serum levels were near or below the level of quantifiability for both agents.", + "Adaptation, Psychological\nAdministration, Oral\nAdult\nAntidepressive Agents, Tricyclic\nCapsules\nData Interpretation, Statistical\nDepression, Postpartum\nDouble-Blind Method\nFemale\nHumans\nInfant, Newborn\nMiddle Aged\nNortriptyline\nPatient Dropouts\nSertraline\nSurveys and Questionnaires\nTime Factors\nTreatment Outcome" + ], + "sentences": [ + "ref-id: L11878; title: FDA Approved Products: Nortriptyline oral capsules and oral solution; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/018012s27lbl.pdf; parent_key: DB00540.", + "ref-id: L9842; title: FDA Approved Drug Products: Complera (Emtricitabine, Rilpivirine, Tenofovir Disoproxil Fumarate) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202123s029lbl.pdf; parent_key: DB00879.", + "ref-id: L1394; title: Pirlindole in the Treatment of Depression and Fibromyalgia Syndrome; url: https://www.researchgate.net/publication/51605654_Pirlindole_in_the_Treatment_of_Depression_and_Fibromyalgia_Syndrome; parent_key: DB09244.", + "ref-id: L12153; title: NIH StatPearls: Cholesterol levels; url: https://www.ncbi.nlm.nih.gov/books/NBK542294/; parent_key: DB11936.", + "ref-id: L12930; title: FDA Approved Drug Products: Epiduo (adapalene and benzoyl peroxide), gel; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207917Orig1s000lbl.pdf; parent_key: DB00210.", + "ref-id: L1716; title: randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer; url: https://academic.oup.com/annonc/article/28/2/285/2676905; parent_key: DB06263.", + "ref-id: L1317; title: The effect of melperone, an atypical antipsychotic drug, on cognitive function in schizophrenia; url: https://www.sciencedirect.com/science/article/pii/S0920996401003292; parent_key: DB09224.", + "ref-id: L1395; title: Hypertensive effect and cheese; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738414/; parent_key: DB09244.", + "ref-id: L4841; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01818492; parent_key: DB14724.", + "ref-id: L13691; title: FDA Approved Drug Products: Spinraza (nusinersen) for intrathecal injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209531s007s008lbl.pdf; parent_key: DB13161.", + "ref-id: L2854; title: Final Report on the Safety Assessment of Quaternium-18, Quaternium-18 Hectorite, and Quaternium-18 Bentonite; url: http://journals.sagepub.com/doi/pdf/10.3109/10915818209013148; parent_key: DB11305.", + "ref-id: L14114; title: FDA Approved Drug Products: Tauvid (flortaucipir F-18) injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212123s000lbl.pdf; parent_key: DB14914.", + "ref-id: L139; title: Antimicrobial agents and Chemotherapy; url: http://aac.asm.org/cgi/content/full/44/7/1925; parent_key: DB06696.", + "ref-id: L852; title: American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017.; url: http://hcvguidelines.org/full-report-view; parent_key: DB11575.", + "ref-id: L5314; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT03172208; parent_key: DB06081.", + "ref-id: L1434; title: Acute Toxicity From Intravenous Use of the Tricyclic Antidepressant Tianeptine; url: https://academic.oup.com/jat/article-abstract/41/6/547/3852120?redirectedFrom=fulltext; parent_key: DB09289.", + "ref-id: L9188; title: Sertraline pathway; url: https://www.pharmgkb.org/pathway/PA166181117; parent_key: DB01104.", + "ref-id: L1611; title: Drug dosing in renal insufficiency; url: https://books.google.ca/books?id=OavnCAAAQBAJ&pg=PA603&lpg=PA603&dq=tyropanoate+sodium+drug+information&source=bl&ots=lgdOlC83fh&sig=hX_ooOrR9qAoQvhVK-AMyJiP4ts&hl=en&sa=X&ved=0ahUKEwi80sKBouDZAhUT2WMKHRnDA3E4ChDoAQg4MAQ#v=onepage&q=tyropanoate%20sodium%20drug%20information&f=false; parent_key: DB09340.", + "ref-id: L1720; title: Tibolone for Postmenopausal Women: Systematic Review of Randomized Trials; url: https://academic.oup.com/jcem/article/87/1/16/2846489; parent_key: DB09070.", + "ref-id: L4834; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02181660; parent_key: DB12141.", + "ref-id: L1864; title: The effect of tildrakizumab, a high-affinity, selective anti-IL23p19 monoclonal antibody (mAb), on cytochrome P450 (CYP) metabolism; url: http://www.jaad.org/article/S0190-9622(17)31465-2/fulltext; parent_key: DB14004.", + "ref-id: L4835; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02456883; parent_key: DB12141.", + "ref-id: L2965; title: Enhancement of Tumor Response to -Radiation by an Inhibitor of Cyclooxygenase-2 Enzyme; url: https://www.researchgate.net/publication/31132809_Enhancement_of_Tumor_Response_to_-Radiation_by_an_Inhibitor_of_Cyclooxygenase-2_Enzyme; parent_key: DB14059.", + "ref-id: L2930; title: AstraZeneca: ZS-9 (sodium zirconium cyclosilicate) Phase III long-term safety and efficacy data presented at ASN Kidney Week 2017; url: https://www.astrazeneca.com/media-centre/medical-releases/zs-9-sodium-zirconium-cyclosilicate-phase-iii-long-term-safety-and-efficacy-data-presented-at-asn-kidney-week-201702112017.html; parent_key: DB14048.", + "ref-id: L2097; title: Zinc, future mono/adjunctive therapy for depression: Mechanisms of antidepressant action; url: https://www.sciencedirect.com/science/article/abs/pii/S1734114015000274; parent_key: DB01593.", + "ref-id: L1855; title: Effect of Polysorbate 80 Quality on Photostability of a Monoclonal Antibody; url: https://www.ncbi.nlm.nih.gov/pubmed/22362139; parent_key: DB11063.", + "ref-id: L1630; title: Severe depression caused by reserpine; url: https://www.semanticscholar.org/paper/Severe-depression-caused-by-reserpine./3e0338937c0882d799d2374efac9aa93c0515995; parent_key: DB09363.", + "ref-id: L2208; title: Chapter 16. Zinc; url: http://www.fao.org/docrep/004/y2809e/y2809e0m.htm; parent_key: DB14487.", + "ref-id: L2843; title: JAMA Network: Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine; url: https://jamanetwork.com/journals/jama/article-abstract/2681193?redirect=true; parent_key: DB14041.", + "ref-id: L11899; title: Product monograph: Nortriptyline tablets; url: https://pdf.hres.ca/dpd_pm/00001266.PDF; parent_key: DB00540.", + "ref-id: L14096; title: FDA Approved Drug Products: Cerianna (fluoroestradiol F 18) for intravenous injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212155s000lbl.pdf; parent_key: DB15690.", + "ref-id: L1168; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/record/NCT02612298?view=results; parent_key: DB09204.", + "ref-id: L8732; title: EMA Approved Drugs: Gabapentin; url: https://www.ema.europa.eu/en/documents/referral/neurontin-article-30-referral-annex-i-ii-iii_en.pdf; parent_key: DB00996.", + "ref-id: L2354; title: Effect of Pepsin on the Absorption of Food Vitamin B12 and Iron; url: https://academic.oup.com/ajcn/article-abstract/20/6/636/4787901?redirectedFrom=PDF; parent_key: DB13198.", + "ref-id: L7856; title: Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids; url: https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.8b00064; parent_key: DB01438.", + "ref-id: L13772; title: FDA Approved Drug Products: ONGENTYS (opicapone) capsules, for oral use; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212489s000lbl.pdf; parent_key: DB11632.", + "ref-id: L5170; title: The binding of Clotrimazole to the proteins of human serum; url: https://www.researchgate.net/publication/225525540_The_binding_of_Clotrimazole_to_the_proteins_of_human_serum; parent_key: DB00257.", + "ref-id: L14024; title: FDA Approved Drug Products: Vusion (miconazole nitrate, zinc oxide, white petrolatum) topical ointment; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021026s013lbl.pdf; parent_key: DB01110.", + "ref-id: L1876; title: The Effects of Tibolone in Older Postmenopausal Women; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684062/; parent_key: DB09070.", + "ref-id: L342; title: FDA data; url: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/Darvocet-N_July2009.pdf; parent_key: DB00647.", + "ref-id: L7982; title: Canadian Agency for Drugs and Technologies in Health: Dicyclomine for Gastrointestinal Conditions: A Review of the Clinical Effectiveness, Safety, and Guidelines; url: https://www.ncbi.nlm.nih.gov/books/NBK350056/pdf/Bookshelf_NBK350056.pdf; parent_key: DB00804.", + "ref-id: L5876; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02499146; parent_key: DB09073.", + "ref-id: L2208; title: Chapter 16. Zinc; url: http://www.fao.org/docrep/004/y2809e/y2809e0m.htm; parent_key: DB01593.", + "ref-id: L1136; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/results/NCT02411929?sect=Xgf0156#outcome10; parent_key: DB11827.", + "ref-id: L7673; title: Sodium fluoride F-18 injection, DailyMed; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=96e61ba1-30ca-4844-b503-056afd247e69; parent_key: DB09325.", + "ref-id: L5798; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01123486; parent_key: DB00327.", + "ref-id: L2589; title: An evaluation of the effect ov lanolin in healing nipple injuries; url: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-21002008000100002; parent_key: DB11112.", + "ref-id: L12882; title: FDA Approved Drug Products: Benicar (olmesartan medoxomil) oral tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021286s040lbl.pdf; parent_key: DB00275.", + "ref-id: L2097; title: Zinc, future mono/adjunctive therapy for depression: Mechanisms of antidepressant action; url: https://www.sciencedirect.com/science/article/abs/pii/S1734114015000274; parent_key: DB14487.", + "ref-id: L2518; title: Norepinephrine-dopamine reuptake inhibitor; url: https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/norepinephrine-dopamine-reuptake-inhibitor; parent_key: DB11584." + ] + }, + { + "example_idx": 69, + "anchor_id": 15162859634981291137, + "positive_id": 2150985440034370662, + "join_paths": [ + [ + 15, + 49, + 0.3203125 + ], + [ + 15, + 26, + 0.318359375 + ], + [ + 15, + 3, + 0.314453125 + ], + [ + 15, + 4, + 0.3125 + ], + [ + 15, + 14, + 0.3125 + ] + ], + "rows": [ + "On the basis of peripheral (nonbrain) neuroendocrine findings in subjects with posttraumatic stress disorder (PTSD), it has been hypothesized that these individuals also have a greater central (brain) sensitivity to glucocorticoids.", + "In nonpsychiatric subjects, it has been found that working and declarative memory performance is selectively impaired by acute glucocorticoid administration.", + "We hypothesized that subjects with PTSD, as compared to nonpsychiatric controls, would show greater impairments in verbal declarative memory and working memory, but not attention, following exogenous glucocorticoid administration.", + "These data are part of a larger study using functional neuroimaging and peripheral HPA axis measures in these same subjects.", + "Subjects underwent a 0.5-mg dexamethasone suppression test and measurement of basal cortisol, basal plasma lymphocyte glucocorticoid receptor number, and postdexamethasone cortisol on a separate day.", + "Under double-blind randomized crossover conditions, 17-mg hydrocortisone or placebo was administered by intravenous (i.v.)", + "bolus to 15 medication-free PTSD subjects (4 female) and 12 nonpsychiatric control subjects (4 female) matched by age, sex, and education level.", + "Participants then underwent positron emission tomography (PET) scanning and 90 min after the initial drug/placebo administration, cognitive testing was then performed.", + "By repeated measures ANCOVA (covaried for baseline performance on that neuropsychological test), neither attention tasks of digit span forward nor backward showed significant change.", + "However, there were significant drug (F = 17.644, df = 1,25 P < 0.001), group (F = 4.383, df = 1,25 P = 0.048), and drug by group interactions (F = 4.756, df = 1,25 P = 0.040) for verbal declarative memory.", + "By t-test, there was not a difference in baseline performance on this measure between subject groups.", + "The subject group with PTSD experienced a greater decline in verbal declarative memory performance following hydrocortisone administration.", + "For working memory, there were significant group (F = 6.048, df = 1,25 P = 0.022) and drug by group interactions (F = 6.048, df = 1,25 P = 0.022) for verbal declarative memory.", + "By t-test, there was not a difference in baseline performance on this measure between subject groups.", + "The hydrocortisone administration led to impairment in working memory in the group of subjects with PTSD, but not in the control subject group.", + "Exploratory correlations between percent cortisol suppression following dexamethasone and baseline plasma lymphocyte glucocorticoid receptor number with declarative and working memory measures among subject groups separately and in a combined way revealed a negative correlation between lymphocyte glucocorticoid receptor density and working memory (r = -0.54, df = 25, P = 0.008).", + "Brain sensitivity to glucocorticoids appears to be greater in subjects with PTSD.", + "Heightened vulnerability of declarative memory in subjects with PTSD may indicate hippocampal involvement, whereas working memory vulnerability suggests additional brain regions (prefrontal, cingulate, temporal, and parietal cortices) and neurotransmitter systems (dopamine and serotonin) particularly sensitive to glucocorticoids in persons with PTSD.", + "Adult\nAttention\nCognition\nDouble-Blind Method\nFemale\nHumans\nHydrocortisone\nHypothalamo-Hypophyseal System\nInjections, Intravenous\nLymphocytes\nMale\nMemory, Short-Term\nMiddle Aged\nNeuropsychological Tests\nReceptors, Glucocorticoid\nStress Disorders, Post-Traumatic" + ], + "sentences": [ + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB14631.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; position: 5; parent_key: DB01395.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB08347.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01130.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; parent_key: DB05423.", + "id: BE0009742; name: Matrix metalloproteinase-25; organism: Humans; known_action: unknown; position: 2; parent_key: DB13873.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00838.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB07080.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 11; parent_key: DB01645.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: unknown; position: 5; parent_key: DB00231.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB00696.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00687.", + "id: BE0000640; name: Glutamate receptor 1; organism: Humans; known_action: unknown; parent_key: DB06247.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 25; parent_key: DB01026.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00240.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB01708.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00620.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; position: 6; parent_key: DB00367.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB15566.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01384.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB14669.", + "id: BE0000384; name: Neurokinin 1 receptor; organism: Humans; known_action: unknown; parent_key: DB05466.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00896.", + "id: BE0009742; name: Matrix metalloproteinase-25; organism: Humans; known_action: yes; position: 20; parent_key: DB00786.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB08867.", + "id: BE0002088; name: Estrogen-related receptor gamma; organism: Humans; known_action: yes; parent_key: DB00255.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB13158.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB12582.", + "id: BE0003848; name: Nuclear receptor subfamily 1 group I member 3; organism: Humans; known_action: unknown; position: 1; parent_key: DB01889.", + "id: BE0003848; name: Nuclear receptor subfamily 1 group I member 3; organism: Humans; known_action: unknown; position: 3; parent_key: DB04540.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: no; position: 3; parent_key: DB14583.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01013.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00834.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB00431.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB08604.", + "id: BE0009370; name: Thiol groups; organism: Humans; known_action: yes; position: 1; parent_key: DB13960.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB00351.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00223.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 4; parent_key: DB08906.", + "id: BE0000203; name: Gonadotropin-releasing hormone receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB06699.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB00834.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 4; parent_key: DB01234.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 16; parent_key: DB00655.", + "id: BE0009339; name: Free radicals; organism: Humans; known_action: yes; position: 3; parent_key: DB14003.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB14544.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; parent_key: DB00959.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00288.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB14543.", + "id: BE0009159; name: Transient receptor potential cation channel subfamily V member 4; organism: Humans; known_action: unknown; position: 7; parent_key: DB11148.", + "id: BE0000794; name: Glucocorticoid receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB13003." + ] + }, + { + "example_idx": 70, + "anchor_id": 5148478187420667668, + "positive_id": 11276228325273544719, + "join_paths": [ + [ + 1, + 28, + 0.255859375 + ], + [ + 1, + 46, + 0.25 + ], + [ + 1, + 15, + 0.2490234375 + ], + [ + 1, + 2, + 0.248046875 + ], + [ + 1, + 10, + 0.248046875 + ] + ], + "rows": [ + "Disulfiram (Antabuse) is used for aversive treatment of alcohol dependence with good effects.", + "Through inhibition of aldehyde dehydrogenase, disulfiram heightens serum aldehyde concentration after alcohol ingestion and causes aversive disulfiram-ethanol reaction.", + "Typical symptoms of this reaction include flushing, nausea, dyspnea, tremor, and confusion, which are usually self-limiting.", + "However, severe life-threatening arterial hypotension sometimes develops.", + "We report here a patient with generalized flushing, tremor, and refractive hypotension after ingestion of alcohol 18 hours after disulfiram treatment.", + "Initial volume resuscitation and dopamine infusion failed to restore the blood pressure.", + "Noradrenaline was given and the blood pressure returned to normal range.", + "This case illustrates the intensity of disulfiram-ethanol reaction and underscores the advantageous use of noradrenaline in patients in such a critical condition.", + "Adult\nAlcohol Deterrents\nDisulfiram\nEthanol\nHumans\nHypotension\nMale\nNorepinephrine\nVasoconstrictor Agents" + ], + "sentences": [ + "drugbank-id: DB00822; name: Disulfiram; description: The metabolism of Disulfiram can be increased when combined with Betamethasone phosphate.; parent_key: DB14669.", + "drugbank-id: DB00898; name: Ethanol; description: The risk or severity of hypotension and orthostatic hypotension can be increased when Ethanol is combined with Quinethazone.; parent_key: DB01325.", + "drugbank-id: DB00822; name: Disulfiram; description: The metabolism of Disulfiram can be increased when combined with Golimumab.; parent_key: DB06674.", + "drugbank-id: DB00368; name: Norepinephrine; description: The serum concentration of Dofetilide can be increased when it is combined with Norepinephrine.; parent_key: DB00204.", + "drugbank-id: DB09118; name: Stiripentol; description: The serum concentration of S,R-Warfarin alcohol can be increased when it is combined with Stiripentol.; parent_key: DB08736.", + "drugbank-id: DB00822; name: Disulfiram; description: The serum concentration of Lobucavir can be increased when it is combined with Disulfiram.; parent_key: DB12531.", + "drugbank-id: DB00822; name: Disulfiram; description: The metabolism of Estradiol valerate can be decreased when combined with Disulfiram.; parent_key: DB13956.", + "drugbank-id: DB00822; name: Disulfiram; description: The therapeutic efficacy of Carisbamate can be decreased when used in combination with Disulfiram.; parent_key: DB12338.", + "drugbank-id: DB09330; name: Osimertinib; description: The serum concentration of Osimertinib can be increased when it is combined with Erythromycin.; parent_key: DB00199.", + "drugbank-id: DB00368; name: Norepinephrine; description: The serum concentration of Norepinephrine can be increased when it is combined with Imatinib.; parent_key: DB00619.", + "drugbank-id: DB00822; name: Disulfiram; description: The therapeutic efficacy of Methsuximide can be decreased when used in combination with Disulfiram.; parent_key: DB05246.", + "drugbank-id: DB00368; name: Norepinephrine; description: The risk or severity of adverse effects can be increased when Norepinephrine is combined with Guanfacine.; parent_key: DB01018.", + "drugbank-id: DB00368; name: Norepinephrine; description: The excretion of Varenicline can be decreased when combined with Norepinephrine.; parent_key: DB01273.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Disulfiram is combined with Imipramine.; parent_key: DB00458.", + "drugbank-id: DB00306; name: Talbutal; description: The serum concentration of Methyclothiazide can be increased when it is combined with Talbutal.; parent_key: DB00232.", + "drugbank-id: DB00822; name: Disulfiram; description: The serum concentration of 9-Deazaguanine can be increased when it is combined with Disulfiram.; parent_key: DB04356.", + "drugbank-id: DB00368; name: Norepinephrine; description: The risk or severity of hypertension can be increased when Norepinephrine is combined with Rescinnamine.; parent_key: DB01180.", + "drugbank-id: DB00368; name: Norepinephrine; description: The serum concentration of Norepinephrine can be increased when it is combined with Baricitinib.; parent_key: DB11817.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Disulfiram is combined with Vandetanib.; parent_key: DB05294.", + "drugbank-id: DB00368; name: Norepinephrine; description: The serum concentration of Norepinephrine can be increased when it is combined with Dinoprostone.; parent_key: DB00917.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Disulfiram is combined with Nizofenone.; parent_key: DB13546.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Disulfiram is combined with Levosimendan.; parent_key: DB00922.", + "drugbank-id: DB00822; name: Disulfiram; description: The serum concentration of Proxyphylline can be increased when it is combined with Disulfiram.; parent_key: DB13449.", + "drugbank-id: DB00368; name: Norepinephrine; description: The risk or severity of hypertension can be increased when Norepinephrine is combined with Benorilate.; parent_key: DB13657.", + "drugbank-id: DB10719; name: Pascopyrum smithii pollen; description: The risk of a hypersensitivity reaction to Pascopyrum smithii pollen is increased when it is combined with Bufuralol.; parent_key: DB06726.", + "drugbank-id: DB13766; name: Lidoflazine; description: The risk or severity of hypotension can be increased when Propiomazine is combined with Lidoflazine.; parent_key: DB00777.", + "drugbank-id: DB00822; name: Disulfiram; description: The metabolism of Disulfiram can be decreased when combined with Medical Cannabis.; parent_key: DB14009.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Hyoscyamine is combined with Disulfiram.; parent_key: DB00424.", + "drugbank-id: DB00822; name: Disulfiram; description: The therapeutic efficacy of Sulthiame can be decreased when used in combination with Disulfiram.; parent_key: DB08329.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Disulfiram is combined with Ranolazine.; parent_key: DB00243.", + "drugbank-id: DB09230; name: Azelnidipine; description: The risk or severity of hypotension can be increased when Chlorpromazine is combined with Azelnidipine.; parent_key: DB00477.", + "drugbank-id: DB00822; name: Disulfiram; description: The serum concentration of Acefylline can be increased when it is combined with Disulfiram.; parent_key: DB13573.", + "drugbank-id: DB00822; name: Disulfiram; description: The metabolism of Hydrocortisone acetate can be decreased when combined with Disulfiram.; parent_key: DB14539.", + "drugbank-id: DB11715; name: Bapineuzumab; description: The risk or severity of adverse effects can be increased when Abciximab is combined with Bapineuzumab.; parent_key: DB00054.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Disulfiram is combined with Bencyclane.; parent_key: DB13488.", + "drugbank-id: DB00822; name: Disulfiram; description: Vinblastine may decrease the excretion rate of Disulfiram which could result in a higher serum level.; parent_key: DB00570.", + "drugbank-id: DB00988; name: Dopamine; description: The risk or severity of adverse effects can be increased when Hyaluronidase is combined with Dopamine.; parent_key: DB14740.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of adverse effects can be increased when Cefaloridine is combined with Disulfiram.; parent_key: DB09008.", + "drugbank-id: DB00368; name: Norepinephrine; description: The serum concentration of Norepinephrine can be increased when it is combined with Apalutamide.; parent_key: DB11901.", + "drugbank-id: DB00822; name: Disulfiram; description: The metabolism of Disulfiram can be increased when combined with Fluprednidene.; parent_key: DB08970.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Protriptyline is combined with Disulfiram.; parent_key: DB00344.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Disulfiram is combined with Clemastine.; parent_key: DB00283.", + "drugbank-id: DB00822; name: Disulfiram; description: Indomethacin may decrease the excretion rate of Disulfiram which could result in a higher serum level.; parent_key: DB00328.", + "drugbank-id: DB00822; name: Disulfiram; description: The risk or severity of QTc prolongation can be increased when Disulfiram is combined with Butriptyline.; parent_key: DB09016.", + "drugbank-id: DB11470; name: Tildipirosin; description: The serum concentration of S,R-Warfarin alcohol can be increased when it is combined with Tildipirosin.; parent_key: DB08736.", + "drugbank-id: DB00822; name: Disulfiram; description: The therapeutic efficacy of Zonisamide can be decreased when used in combination with Disulfiram.; parent_key: DB00909.", + "drugbank-id: DB00822; name: Disulfiram; description: The metabolism of Quinacrine can be decreased when combined with Disulfiram.; parent_key: DB01103.", + "drugbank-id: DB00368; name: Norepinephrine; description: The risk or severity of adverse effects can be increased when Norepinephrine is combined with 9-Deazaguanine.; parent_key: DB04356.", + "drugbank-id: DB00368; name: Norepinephrine; description: The risk or severity of adverse effects can be increased when Norepinephrine is combined with Lisofylline.; parent_key: DB12406.", + "drugbank-id: DB06725; name: Lornoxicam; description: The risk or severity of bleeding and hemorrhage can be increased when Lornoxicam is combined with Urokinase.; parent_key: DB00013." + ] + }, + { + "example_idx": 71, + "anchor_id": 14928685875577655724, + "positive_id": 7044465838894004433, + "join_paths": [ + [ + 6, + 6, + 0.265625 + ], + [ + 6, + 39, + 0.265625 + ], + [ + 6, + 3, + 0.251953125 + ], + [ + 6, + 31, + 0.25 + ], + [ + 6, + 49, + 0.2431640625 + ] + ], + "rows": [ + "An 81-year-old woman had pneumonia caused by Streptococcus pneumoniae (levofloxacin Etest minimum inhibitory concentration [MIC] 1.5 microg/ml) and was treated with intravenous gatifloxacin 200 mg/day.", + "After 3 days of therapy, repeat sputum cultures were positive for S. pneumoniae, which was resistant to levofloxacin (Etest MIC > 32 microg/ml).", + "The isolate obtained before therapy showed a preexisting parC mutation of aspartic acid-83 to asparagine (Asp83-->Asn), and the isolate obtained during therapy showed an acquired gyrA mutation from serine-81 to phenylalanine (Ser81-->Phe) and a second parC mutation from lysine-137 to Asn (Lys137-->Asn).", + "Both isolates were the same strain, as determined with pulsed-field gel electrophoresis.", + "This case demonstrates the potential for resistance to emerge during 8-methoxy fluoroquinolone therapy for fluoroquinolone-susceptible S. pneumoniae with a preexisting parC mutation.", + "Additional clinical failures with a fluoroquinolone may occur unless these first-step parC mutants can be identified to assist clinicians in selecting appropriate antimicrobial therapy.", + "Aged, 80 and over\nDNA Gyrase\nDNA Topoisomerase IV\nDrug Resistance\nFemale\nFluoroquinolones\nGatifloxacin\nHumans\nMutation\nPneumococcal Infections\nStreptococcus pneumoniae\nTreatment Failure" + ], + "sentences": [ + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB01155.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB01165.", + "id: BE0000471; name: Gamma-aminobutyric acid receptor subunit alpha-5; organism: Humans; known_action: unknown; parent_key: DB05087.", + "id: BE0003724; name: DNA gyrase subunit A; organism: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4); known_action: yes; position: 4; parent_key: DB06771.", + "id: BE0004632; name: Serine/threonine-protein kinase TAO2; organism: Humans; known_action: unknown; position: 32; parent_key: DB12010.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; position: 2; parent_key: DB00487.", + "id: BE0004950; name: DNA topoisomerase 1; organism: Staphylococcus aureus; known_action: unknown; position: 4; parent_key: DB00487.", + "id: BE0000799; name: DNA gyrase subunit B; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04395.", + "id: BE0008382; name: DNA gyrase subunit A; organism: Escherichia coli (strain K12); known_action: yes; position: 5; parent_key: DB11943.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB01137.", + "id: BE0000971; name: DNA topoisomerase 1; organism: Humans; known_action: yes; position: 1; parent_key: DB01030.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB01208.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB00467.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; position: 6; parent_key: DB00537.", + "id: BE0002192; name: Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB00126.", + "id: BE0000642; name: 72 kDa type IV collagenase; organism: Humans; known_action: unknown; parent_key: DB05387.", + "id: BE0003416; name: Transient receptor potential cation channel subfamily V member 3; organism: Humans; known_action: unknown; position: 36; parent_key: DB09061.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; position: 1; parent_key: DB12808.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB00218.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; position: 1; parent_key: DB09047.", + "id: BE0001950; name: DNA topoisomerase 1; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB01812.", + "id: BE0002346; name: Gamma-aminobutyric acid receptor subunit beta-2; organism: Humans; known_action: unknown; position: 4; parent_key: DB01381.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; position: 1; parent_key: DB04576.", + "id: BE0009384; name: Serine/threonine-protein kinase 3; organism: Humans; known_action: unknown; position: 23; parent_key: DB12010.", + "id: BE0000971; name: DNA topoisomerase 1; organism: Humans; known_action: yes; parent_key: DB00762.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB00978.", + "id: BE0003725; name: DNA gyrase subunit B; organism: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4); known_action: yes; position: 2; parent_key: DB01044.", + "id: BE0009383; name: Serine/threonine-protein kinase 24; organism: Humans; known_action: unknown; position: 22; parent_key: DB12010.", + "id: BE0008382; name: DNA gyrase subunit A; organism: Escherichia coli (strain K12); known_action: unknown; position: 9; parent_key: DB00537.", + "id: BE0000799; name: DNA gyrase subunit B; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03966.", + "id: BE0001950; name: DNA topoisomerase 1; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04205.", + "id: BE0003724; name: DNA gyrase subunit A; organism: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4); known_action: yes; position: 1; parent_key: DB01044.", + "id: BE0008387; name: DNA gyrase subunit A; organism: Bacillus subtilis (strain 168); known_action: unknown; position: 12; parent_key: DB00537.", + "id: BE0000971; name: DNA topoisomerase 1; organism: Humans; known_action: unknown; parent_key: DB04690.", + "id: BE0002665; name: DNA gyrase subunit B; organism: Thermus thermophilus; known_action: unknown; parent_key: DB01942.", + "id: BE0002346; name: Gamma-aminobutyric acid receptor subunit beta-2; organism: Humans; known_action: yes; position: 1; parent_key: DB00818.", + "id: BE0001950; name: DNA topoisomerase 1; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB01643.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB00685.", + "id: BE0000799; name: DNA gyrase subunit B; organism: Escherichia coli (strain K12); known_action: yes; position: 1; parent_key: DB00817.", + "id: BE0004950; name: DNA topoisomerase 1; organism: Staphylococcus aureus; known_action: unknown; position: 5; parent_key: DB01051.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB00365.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; position: 3; parent_key: DB06771.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; position: 1; parent_key: DB00827.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB01059.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; parent_key: DB01405.", + "id: BE0000366; name: DNA gyrase subunit A; organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); known_action: yes; position: 1; parent_key: DB12924.", + "id: BE0004951; name: DNA topoisomerase 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB00970.", + "id: BE0002388; name: DNA gyrase subunit B; organism: Staphylococcus aureus; known_action: yes; parent_key: DB01051.", + "id: BE0000799; name: DNA gyrase subunit B; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB05488.", + "id: BE0008385; name: DNA gyrase subunit A; organism: Staphylococcus aureus; known_action: unknown; position: 15; parent_key: DB00537." + ] + }, + { + "example_idx": 72, + "anchor_id": 8350474260470306857, + "positive_id": 1655144701311155044, + "join_paths": [ + [ + 4, + 20, + 0.1904296875 + ], + [ + 9, + 25, + 0.1708984375 + ], + [ + 6, + 20, + 0.1689453125 + ], + [ + 9, + 39, + 0.16796875 + ], + [ + 9, + 11, + 0.1650390625 + ] + ], + "rows": [ + "The purpose of the present study was to investigate the role of multidrug resistance-associated protein 4 (MRP4) in the tubular secretion of cephalosporin antibiotics.", + "Most of the injectable cephalosporins have an inhibitory effect on the ATP-dependent uptake of [(3)H]dehydroepiandrosterone sulfate by membrane vesicles expressing hMRP4, whereas cephaloridine, cefsulodin, and cefepime do not.", + "Aminocephalosporins have a weak inhibitory effect.", + "Significant ATP-dependent transport of ceftizoxime (K(m), 18 microM), cefazolin (K(m), 80 microM), cefotaxime, and cefmetazole has been observed only in the membrane vesicles expressing hMRP4.", + "Ceftizoxime and cefazolin were given by a constant intravenous infusion to wild-type and Mrp4(-/-) mice.", + "The steady-state plasma concentrations of ceftizoxime and cefazolin were unchanged in Mrp4(-)(/)(-) mice.", + "The urinary recovery of ceftizoxime was significantly reduced in Mrp4(-/-) mice, whereas it was unchanged for cefazolin.", + "The kidney-to-plasma concentration ratio of ceftizoxime and cefazolin was increased 2.0- and 2.7-fold in Mrp4(-/-) mice, respectively; thus, the renal clearance with regard to the kidney concentration was reduced in Mrp4(-/-) mice, to 7.5 and 34% of the corresponding control values, respectively.", + "These results suggest that Mrp4 is involved in the tubular secretion of ceftizoxime and cefazolin, in concert with basolateral uptake transporters.", + "Animals\nBiological Transport\nCefazolin\nCeftizoxime\nKidney\nKidney Tubules, Proximal\nMice\nMultidrug Resistance-Associated Proteins" + ], + "sentences": [ + "name: Viva; ingredients: Polysorbate 80; parent_key: DB11063.", + "name: Ceprotin; ingredients: Protein C; parent_key: DB11312.", + "name: Maxipime for Injection-pws IV 2gm; ingredients: Cefepime; parent_key: DB01413.", + "name: Cefotaxime for Injection USP; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Multiple Vitamin Plus Minerals Tab; ingredients: Ascorbic acid + Calcium + Copper + Cyanocobalamin + Ergocalciferol + Ferrous sulfate anhydrous + Nicotinamide + Pantothenic acid + Potassium Iodide + Pyridoxine + Riboflavin + Thiamine + Vitamin A; parent_key: DB02701.", + "name: Kcentra; ingredients: Coagulation Factor IX Human + Coagulation factor VII human + Coagulation factor X human + Protein C + Protein S human + Prothrombin; parent_key: DB13149.", + "name: Cefazolin for Injection USP; ingredients: Cefazolin; parent_key: DB01327.", + "name: Red Kidney Bean; ingredients: Kidney bean; parent_key: DB10639.", + "name: Claforan Pws Inj 1.0gm/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Sodium Fluoride F18; ingredients: Fluoride ion F-18; parent_key: DB09398.", + "name: Cerianna; ingredients: Fluoroestradiol F-18; parent_key: DB15690.", + "name: Cefazolin for Injection; ingredients: Cefazolin; parent_key: DB01327.", + "name: Claforan - Pws Inj 500mg/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Comvax; ingredients: Haemophilus influenzae type B capsular polysaccharide meningococcal outer membrane protein conjugate antigen + Hepatitis B Vaccine (Recombinant); parent_key: DB10342.", + "name: Kabiven; ingredients: Alanine + Arginine + Aspartic acid + Calcium chloride + D-glucose + Glutamic acid + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Magnesium sulfate + Methionine + Phenylalanine + Potassium chloride + Proline + Serine + Sodium acetate + Sodium glycerophosphate + Soybean oil + Threonine + Tryptophan + Tyrosine + Valine; parent_key: DB09422.", + "name: Claforan 0.5gm/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Multitrace -4; ingredients: Chromic chloride + Cupric sulfate + Manganese + Zinc sulfate; parent_key: DB06757.", + "name: Mixed Vespid Hymenoptera Venom Multidose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11031.", + "name: Tauvid; ingredients: Flortaucipir F-18; parent_key: DB14914.", + "name: Cefepime; ingredients: Cefepime; parent_key: DB01413.", + "name: Cefizox; ingredients: Ceftizoxime; parent_key: DB01332.", + "name: Navy Beans; ingredients: Kidney bean; parent_key: DB10639.", + "name: Plasma Protein Fraction (human) Protenate; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Medi Hydro DP Cleanser; ingredients: Allantoin + Sodium lauryl sulfate + Titanium dioxide; parent_key: DB00815.", + "name: Claforan - Pws Inj 2.0g/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Cefazolin; ingredients: Cefazolin; parent_key: DB01327.", + "name: Maxipime; ingredients: Cefepime; parent_key: DB01413.", + "name: Claforan 1gm/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Dermagran Moisturizing Spray; ingredients: Pyridoxine + Zinc acetate + Zinc chloride + Zinc sulfate; parent_key: DB09322.", + "name: Claforan Add-vantage Vials 1gm/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Polysorbate; ingredients: Polysorbate 80; parent_key: DB11063.", + "name: IV Solution Stabilizer; ingredients: Polysorbate 80; parent_key: DB11063.", + "name: Claforan - Pws Inj 1.0g/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Cefazolin for Injection, USP; ingredients: Cefazolin; parent_key: DB01327.", + "name: Red Kidney Beans; ingredients: Kidney bean; parent_key: DB10639.", + "name: Livron Plus Ampoule; ingredients: Cyanocobalamin + Ferrous sulfate anhydrous + Nicotinamide + Pyridoxine + Riboflavin + Thiamine; parent_key: DB02701.", + "name: Octaplasma; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Claforan Pws Inj 500mg/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Ancef Inj Pws 10gm/vial USP; ingredients: Cefazolin; parent_key: DB01327.", + "name: Sterile Cefazolin Sodium; ingredients: Cefazolin; parent_key: DB01327.", + "name: Claforan Inj 1gm/add-vantage Vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Ancef Inj Pws 1gm/vial USP; ingredients: Cefazolin; parent_key: DB01327.", + "name: Octaplas; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Apo-cefepime; ingredients: Cefepime; parent_key: DB01413.", + "name: IV Stabilizer; ingredients: Polysorbate 80; parent_key: DB11063.", + "name: Claforan Pws Inj 2.0gm/vial; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Kefzol Add-vantage Inj 500mg/vial; ingredients: Cefazolin; parent_key: DB01327.", + "name: Cefotaxime; ingredients: Cefotaxime; parent_key: DB00493.", + "name: Avitears; ingredients: Polysorbate 80; parent_key: DB11063.", + "name: Pascord 7 0.48mg/2.54cm; ingredients: Aluminum sulfate; parent_key: DB11239." + ] + }, + { + "example_idx": 73, + "anchor_id": 16723122026931919444, + "positive_id": 2550272968719034832, + "join_paths": [ + [ + 2, + 11, + 0.2255859375 + ], + [ + 14, + 15, + 0.220703125 + ], + [ + 2, + 46, + 0.2197265625 + ], + [ + 2, + 0, + 0.21875 + ], + [ + 14, + 31, + 0.21875 + ] + ], + "rows": [ + "Progressive cardiac remodeling is characterized by subsequent chamber hypertrophy, enlargement, and pump dysfunction.", + "It is also associated with increased cardiac fibrosis and matrix turnover.", + "Interestingly, peroxisome proliferator-activated receptor (PPAR) alpha activators reduce cardiac hypertrophy, inflammation, and fibrosis.", + "Little is known about the role of fenofibrates in mediating PPARalpha-independent effects in response to chronic pressure overload (PO).", + "Wild-type and PPARalpha-deficient mice were subjected to chronic PO caused by ascending aortic constriction to test the role of fenofibrates in chronic, progressive cardiac remodeling by a PPARalpha-independent mechanism.", + "Mice were randomized to regular chow or chow-containing fenofibrate (100 mg/kg of body weight per day) for 1 week before and 8 weeks after ascending aortic constriction.", + "In the presence of PPARalpha, wild-type chronic PO mice, treated with fenofibrate, had improved cardiac remodeling.", + "However, PO PPARalpha-deficient mice treated with fenofibrate had increased mortality, significantly adverse left ventricular end diastolic (3.4+/-0.1 versus 4.2+/-0.1 mm) and end systolic (1.5+/-0.2 versus 2.5+/-0.2 mm) dimensions, and fractional shortening (57+/-3% versus 40+/-3%).", + "Fenofibrate also increased myocardial hypertrophy, cardiac fibrosis, and the ratio of matrix metalloproteinase-2/tissue inhibitor of matrix metalloproteinase-2 in PO PPARalpha-deficient mice.", + "Fenofibrate inhibited matrix metalloproteinase activity in vitro and aldosterone-induced increases in extracellular signal-regulated kinase phosphorylation.", + "Thus, fenofibrate improved cardiac remodeling in chronic PO mice.", + "However, in PPARalpha-deficient mice, this chronic PO was exacerbated and associated with increased myocardial fibrosis and altered matrix remodeling.", + "In the absence of PPARalpha, fenofibrates exerts deleterious, pleiotropic myocardial actions.", + "This is an important observation, because PPARalpha agonists are considered possible inhibitory regulators of cardiac remodeling in the remodeled heart.", + "Aldosterone\nAnimals\nCells, Cultured\nChronic Disease\nExtracellular Signal-Regulated MAP Kinases\nFenofibrate\nFibrosis\nHypertension\nHypolipidemic Agents\nKaplan-Meier Estimate\nMatrix Metalloproteinase 2\nMatrix Metalloproteinase 9\nMatrix Metalloproteinase Inhibitors\nMice\nMice, Inbred Strains\nMyocardium\nMyocytes, Cardiac\nPPAR alpha\nPeroxisome Proliferator-Activated Receptors\nPhosphorylation\nTime Factors\nTissue Inhibitor of Metalloproteinases\nVentricular Function, Left" + ], + "sentences": [ + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: yes; parent_key: DB01393.", + "id: BE0002198; name: Amine oxidase [flavin-containing] A; organism: Humans; known_action: no; position: 2; parent_key: DB14914.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 2; parent_key: DB06908.", + "id: BE0001122; name: Transient receptor potential cation channel subfamily A member 1; organism: Humans; known_action: unknown; position: 29; parent_key: DB14011.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: yes; parent_key: DB01132.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB07723.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 11; parent_key: DB00159.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 5; parent_key: DB01708.", + "id: BE0000058; name: Matrix metalloproteinase-9; organism: Humans; known_action: unknown; parent_key: DB03683.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; parent_key: DB06510.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB01252.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; parent_key: DB06521.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB11672.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 22; parent_key: DB00328.", + "id: BE0000291; name: 5-hydroxytryptamine receptor 1A; organism: Humans; known_action: unknown; position: 11; parent_key: DB00696.", + "id: BE0000058; name: Matrix metalloproteinase-9; organism: Humans; known_action: unknown; position: 55; parent_key: DB14533.", + "id: BE0000058; name: Matrix metalloproteinase-9; organism: Humans; known_action: unknown; position: 1; parent_key: DB07285.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; parent_key: DB04971.", + "id: BE0001920; name: Alpha-xylosidase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03434.", + "id: BE0009430; name: Serine/threonine-protein kinase DCLK2; organism: Humans; known_action: unknown; position: 108; parent_key: DB12010.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB07675.", + "id: BE0001425; name: Tubulin alpha-3C/D chain; organism: Humans; known_action: unknown; parent_key: DB03010.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 14; parent_key: DB01118.", + "id: BE0003692; name: Matrix metalloproteinase-14; organism: Humans; known_action: yes; position: 11; parent_key: DB00786.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 21; parent_key: DB00197.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB07208.", + "id: BE0001132; name: Protein kinase C alpha type; organism: Humans; known_action: unknown; position: 1; parent_key: DB11752.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 22; parent_key: DB02709.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 8; parent_key: DB02266.", + "id: BE0000417; name: Glutamate receptor ionotropic, NMDA 2B; organism: Humans; known_action: yes; position: 1; parent_key: DB00949.", + "id: BE0000779; name: Vitamin D3 receptor; organism: Humans; known_action: unknown; parent_key: DB05024.", + "id: BE0000058; name: Matrix metalloproteinase-9; organism: Humans; known_action: unknown; position: 3; parent_key: DB01197.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: yes; position: 3; parent_key: DB01393.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB08402.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 10; parent_key: DB13961.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB07209.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; parent_key: DB06521.", + "id: BE0003703; name: Matrix metalloproteinase-28; organism: Humans; known_action: yes; position: 23; parent_key: DB00786.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; parent_key: DB05854.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 22; parent_key: DB00313.", + "id: BE0003702; name: Matrix metalloproteinase-27; organism: Humans; known_action: yes; position: 22; parent_key: DB00786.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 2; parent_key: DB12007.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: yes; position: 4; parent_key: DB00795.", + "id: BE0000756; name: Dopamine D2 receptor; organism: Humans; known_action: unknown; position: 11; parent_key: DB00715.", + "id: BE0000058; name: Matrix metalloproteinase-9; organism: Humans; known_action: unknown; position: 9; parent_key: DB01017.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB07172.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 4; parent_key: DB11133.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 5; parent_key: DB02746.", + "id: BE0009668; name: Extracellular signal-regulated kinase (ERK); organism: Humans; known_action: unknown; position: 18; parent_key: DB00945.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 18; parent_key: DB09061." + ] + }, + { + "example_idx": 74, + "anchor_id": 14928855469372462923, + "positive_id": 4561082551470598314, + "join_paths": [ + [ + 11, + 8, + 0.1962890625 + ], + [ + 11, + 33, + 0.1962890625 + ], + [ + 7, + 24, + 0.1767578125 + ], + [ + 4, + 9, + 0.1708984375 + ], + [ + 5, + 1, + 0.15625 + ] + ], + "rows": [ + "BACKGROUND: There is no therapeutic intervention that reliably restores smooth muscle contractility for patients with ineffective esophageal motility (IEM).", + "Bethanechol, a direct-acting muscarinic receptor agonist, has been shown in healthy volunteers to produce a significant increase in peristaltic amplitude in the distal esophagus.", + "AIM: To identify whether bethanechol improves smooth muscle contractility and bolus transit in patients with IEM.", + "METHODS: Seven patients diagnosed with severe IEM documented by combined multichannel intraluminal impedance and esophageal manometry were asked to participate.", + "IEM was defined by using the new proposed criteria of greater than or equal to 50% saline swallows with contraction amplitude <30 mm Hg either 5 and/or 10 cm above the lower esophageal sphincter (LES).", + "In the supine position, the patients were given 10 swallows of 5 mL of normal saline then 10 swallows of viscous solution, each 20 to 30 seconds apart.", + "Patients were then given 50 mg oral bethanechol.", + "After 20 and 40 minutes, 5 swallows of saline and viscous solution were repeated.", + "Studies were then analyzed by an investigator blinded to the relationship of bethanechol administration to the swallows.", + "The analysis included measurement of distal esophageal amplitude (DEA) or the mean amplitude at 5 and 10 cm above the LES.", + "RESULTS: The use of bethanechol significantly increased (P<0.05) the esophageal contraction pressures at 5 and 10 cm above the LES.", + "The DEA increased (P<0.05) for liquid and viscous, 20 minutes after its administration.", + "Forty minutes after bethanechol administration, DEA and also individual pressures at 5 and 10 cm above the LES were still increased (P<0.05) for liquid, but only the DEA increased (P<0.05) with viscous solution.", + "There was also a significant increase in complete bolus transit for saline swallows, both 20 and 40 minutes (P=0.03 and 0.01, respectively) after bethanechol.", + "CONCLUSIONS: Oral bethanechol significantly improves contraction pressures and bolus transit in the smooth muscle portion of the esophagus in patients with severe IEM.", + "Adult\nAged\nBethanechol\nDeglutition\nEsophageal Motility Disorders\nFemale\nHumans\nMale\nManometry\nMiddle Aged\nMuscarinic Agonists\nMuscle, Smooth\nPeristalsis" + ], + "sentences": [ + "ref-id: L5443; title: Prosulf (protamine sulfate) 10 mg/ml Solution for Injection; url: https://www.medicines.org.uk/emc/product/8/smpc; parent_key: DB09141.", + "ref-id: L789; title: FDA Monograph: Sodium Citrate Liquid; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eb0bade0-fc86-4bfa-90cc-f0d5f7b4d3a8; parent_key: DB09154.", + "ref-id: L2292; title: Paladin Labs - Product Monograph: SANDOMIGRAN (Pizotifen hydrogen malate 0.5 mg and 1 mg tablets); url: http://www.paladin-labs.com/our_products/Sandomigran_en.pdf; parent_key: DB06153.", + "ref-id: L11944; title: FDA Approved Drug Products: Yaz Ethinylestradiol and Drospirenone Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021676s019lbl.pdf; parent_key: DB00977.", + "ref-id: L6193; title: PRO-TRIAZIDE (Triamterene 50 mg and Hydrochlorothiazide 25 mg) - Product Monograph; url: https://pdf.hres.ca/dpd_pm/00026038.PDF; parent_key: DB00384.", + "ref-id: L2900; title: Significant Drug–Drug Interactions with Antineoplastics; url: https://www.ebi.ac.uk/chembl/target/inspect/CHEMBL1876; parent_key: DB00808.", + "ref-id: L2607; title: Mg Gluconate; url: https://www.drugs.com/ppa/magnesium-gluconate.html; parent_key: DB13749.", + "ref-id: L4645; title: Electronic Medicines Compendium: Primidone 50 mg Tablet Monograph; url: https://www.medicines.org.uk/emc/product/2941/smpc; parent_key: DB00794.", + "ref-id: L5074; title: Drug Scheduling: United States Drug Enforcement Administration (DEA); url: https://www.dea.gov/drug-scheduling; parent_key: DB00683.", + "ref-id: L6778; title: Indomethacin Capsules (25 mg) - FDA Label; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/016059s100lbl.pdf; parent_key: DB00328.", + "ref-id: L1383; title: Determination of azelnidipine by LC–ESI-MS and its application to a pharmacokinetic study in healthy Chinese volunteers; url: http://www.ingentaconnect.com/content/govi/pharmaz/2008/00000063/00000008/art00003?crawler=true; parent_key: DB09230.", + "ref-id: L13014; title: DailyMed: Unapproved label for liquid nitrogen, refrigerated; url: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8519f7b5-2fe2-42e9-8604-431a9ccfc420&type=display; parent_key: DB09152.", + "ref-id: L13841; title: Deciphera phase 1 study results; url: https://www.deciphera.com/wp-content/uploads/2018/10/ESMO-2018-George-et-al.-for-submission-to-ESMO-final.pdf; parent_key: DB14840.", + "ref-id: L2615; title: Feix-Sulfur Liquid; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a00ab0c-eb56-4463-9897-90e521b80db5; parent_key: DB11327.", + "ref-id: L1900; title: Pyrantel, Science Direct; url: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/pyrantel; parent_key: DB11156.", + "ref-id: L2608; title: Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach; url: http://www.jle.com/download/mrh-267774-study_of_magnesium_bioavailability_from_ten_organic_and_inorganic_mg_salts_in_mg_depleted_rats_using_a_stable_isotope_approach--WuiPHn8AAQEAADOFX1sAAAAH-a.pdf; parent_key: DB13749.", + "ref-id: L2670; title: Benzophenone, science direct; url: https://www.sciencedirect.com/topics/neuroscience/benzophenone; parent_key: DB11185.", + "ref-id: L12900; title: FDA Approved Drug Products: Risperdal Consta (risperidone) long-acting intramuscular injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021346s063lbl.pdf; parent_key: DB00734.", + "ref-id: L6520; title: Ketorolac for Pain Management: A Review of the Clinical Evidence); url: https://www.ncbi.nlm.nih.gov/books/NBK254117/pdf/Bookshelf_NBK254117.pdf; parent_key: DB00465.", + "ref-id: L1457; title: Studies on the Metabolic Fate of NZ-105. (I). Absorption, Distribution, Metabolism and Excretion after a Single Administration to Rats.; url: https://www.researchgate.net/publication/273669636_Studies_on_the_Metabolic_Fate_of_NZ-105_I_Absorption_Distribution_Metabolism_and_Excretion_after_a_Single_Administration_to_Rats; parent_key: DB09235.", + "ref-id: L1697; title: Therapeutic effects of mifepristone combined with Gestrinone on patients with endometriosis; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103146/; parent_key: DB11619.", + "ref-id: L9659; title: Lasix Oral (furosemide) Product Monograph; url: http://products.sanofi.ca/en/lasix.pdf; parent_key: DB00695.", + "ref-id: L1323; title: Quantification of selected antidepressants and antipsychotics in clinical samples using chromatographic methods combined with mass spectrometry: A review (2006-2015); url: https://pdfs.semanticscholar.org/7af2/95cd553c0def02c99d390fab51c7b5be8ff7.pdf; parent_key: DB09224.", + "ref-id: L2274; title: Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility.; url: https://www.jove.com/visualize/abstract/19337959/corifollitropin-alfa-long-acting-follicle-stimulating-hormone-agonist; parent_key: DB09066.", + "ref-id: L1949; title: Potassium Hydroxide Liquid; url: https://www.drugs.com/pro/potassium-hydroxide-liquid.html; parent_key: DB11153.", + "ref-id: L1678; title: Toxicokinetics of Mercury after Long-Term Repeated Exposure to Thimerosal-Containing Vaccine; url: https://watermark.silverchair.com/kfr009.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAakwggGlBgkqhkiG9w0BBwagggGWMIIBkgIBADCCAYsGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMW0bWnQIT2cgCI9grAgEQgIIBXConbxAIybSm8nt9sq3XLD6FXwk5iR6JvWmt0TZ_eNo1i23x9WAeA27ZgFUJjbtsNrf_SPnPqljOSDTHviFNpDedT1VXht8CrynwJnGIxKgYSgTlvvLMTp529pd4W1rfpurel-Dtb0SEV2z7S5DC8sgbttUwVZldRaQX-BnhUB80qyNopJumFasQtCI2fv1mVs8_jcnECqFbIHY-QMKCcsSB9VYf1hNwnF0sNqPWBVjl-bP8Za1Wjq01NGA9qQUhdZ92c5jGmyFRBhZdbxmOC-9VzwcefYnWxb3C-5DbmOgg7dy3E9o-7JKuOqJWR4Earir-bepLCUqER5TQwzJ-P3XMEWqkuZeVDC7E5mfneV-uVSk7pFVKxLYfkDxma_e-s0xwm2G0DKCPUG2gAMaOcxTaRM2ybi3dOf-X_Hks3ZhQbocEy3ngvPbkmNmnDGzHK67asKvJr9LN27wFdQ; parent_key: DB11590.", + "ref-id: L1792; title: The Absorption and Excretion of a Liquid Polyethylene Glycol; url: https://www.sciencedirect.com/science/article/pii/S0095955315319119; parent_key: DB11077.", + "ref-id: L2332; title: Muscarinic receptor antagonists for overactive bladder; url: https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1464-410X.2007.07205.x; parent_key: DB12278.", + "ref-id: L1683; title: Thimerosal: Clinical, epidemiologic and biochemical studies; url: https://www.sciencedirect.com/science/article/pii/S0009898115001023; parent_key: DB11590.", + "ref-id: L1521; title: Pipamperone and increased excercise/weight; url: https://databankws.lareb.nl/Downloads/Signals_2017_Pipamperone%20and%20increased%20appetite.pdf; parent_key: DB09286.", + "ref-id: L1504; title: Vaya Direct; url: https://vayadirect.com; parent_key: DB09328.", + "ref-id: L6331; title: Electronic Medicines Compendium: Montelukast 5 mg Chewable Tablets Monograph; url: https://www.medicines.org.uk/emc/product/2710/smpc; parent_key: DB00471.", + "ref-id: L2604; title: Mg products; url: http://www.globalrph.com/magnesium_supplements.htm; parent_key: DB13749.", + "ref-id: L5074; title: Drug Scheduling: United States Drug Enforcement Administration (DEA); url: https://www.dea.gov/drug-scheduling; parent_key: DB00395.", + "ref-id: L1374; title: Relationship between pharmacokinetics and pharmacodynamics of molsidomine and its metabolites in humans; url: http://europepmc.org/abstract/med/3838400; parent_key: DB09282.", + "ref-id: L1376; title: Molsidomine 2/4 mg tablets; url: https://pdfs.semanticscholar.org/3cb7/a1d396f6d523af253581daf8033e64a0cb3f.pdf; parent_key: DB09282.", + "ref-id: L10355; title: Magnesium Sulfate Injection, USP 50%; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019316s024lbl.pdf; parent_key: DB14513.", + "ref-id: L4353; title: Teva Pharmaceuticals USA gained approval to market its generic epinephrine auto-injector in 0.3 mg and 0.15 mg strengths.; url: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm617173.htm; parent_key: DB00668.", + "ref-id: L2012; title: FDA CFR - Code of Federal Regulations Title 21, PART 350: ANTIPERSPIRANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE; url: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=350&showFR=1; parent_key: DB11200.", + "ref-id: L8441; title: The Distribution of Fluoxetine in Human Fluids and Tissues; url: https://watermark.silverchair.com/31-7-409.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlswggJXBgkqhkiG9w0BBwagggJIMIICRAIBADCCAj0GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMxq-BdA0pD4hBv9fbAgEQgIICDi9e5SvYdtSTd4n3-ojFsd3phOj6pqFzsbalEBbPOpwULSMguJn_LLSPIgFAyvDZTzElshjv7v1lNiLqb8oVellZb22LL5Zt_sMLZsh6BITXlS-jG-MAQrwGnqi-ExPTlUm-aehAYMpw7Nx9JHGpAXKF1AkHxZ9EMNd5U24o8BBQLvPbykxmSRb0NRhxqz3lAhGzQHQNzYprgkznEu4MX5QwUYuTmxBgZusq9Actqtixc3hcxmsnygZY5CHQzC2u8lIr6GB8vDT5Pc9rDnYMHRzBlNRAYmxcL-UphitDIKgQ3GGxLDhM6kNaaZGBZpA0zTWUJuXs9YulpoviYcDHkwEae5fclzgF902nxuz7XSYli9cY-mqAnntE8jFn8NVrqVbxFzKr0IRb_MzQCD-WU1XE122FsoG0jKpvhpSOJ0VF2BzuHetWI7y1FiB1BJ8-xtNEf_d_0oIsQbmDhJjjgw7P0H_J6I-Xba3WouJx_cay7oQyTr5B6f_dO9oAoeaHaatNci2zlHoWmsNNRCmMMdwlOAs45z63wihln_w0-PlBppn63qgRMUo-7BFytjAVUl6pyf0JG2MkvtqVHfFQU3n8cYNrfGuYN_VirR4yfviv8c3QpYVHkG56bKuOCRYeGevdftSprL8MWpsOV7kiiYEJEaaJTOgg-BOwAIuXpcQUPcC3xULFqRECDCjuBA0; parent_key: DB00472.", + "ref-id: L12720; title: EMA Summary of product characteristics, Ocaliva (obeticholic acid) 5 and 10 mg oral tablets; url: https://www.ema.europa.eu/en/documents/product-information/ocaliva-epar-product-information_en.pdf; parent_key: DB05990.", + "ref-id: L13859; title: Deciphera phase 3 study results; url: https://www.deciphera.com/wp-content/uploads/2019/11/CTOS-2019-INVICTUS-Oral-Presentation-FINAL_Nov-15.pdf; parent_key: DB14840.", + "ref-id: L4894; title: FDA Approved Drug Products: Apadaz (benzhydrocodone and acetaminophen) tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208653s002s003lbl.pdf; parent_key: DB11712.", + "ref-id: L9413; title: FDA Approved Drug Products: Phenylephrine Ophthalmic Solution; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/207926s002lbl.pdf; parent_key: DB00388.", + "ref-id: L11503; title: Estra-50 (Estradiol pellet) implantable; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=596a20bd-d93d-4c48-e053-2991aa0ad4ca; parent_key: DB00783.", + "ref-id: L1661; title: THIOCOLCHICOSIDE AS MUSCLE RELAXANT: A REVIEW; url: https://www.ijpbs.com/ijpbsadmin/upload/ijpbs_50c8471a463c9.pdf; parent_key: DB11582.", + "ref-id: L5959; title: First Targeted Therapy for Metastatic Bladder Cancer Receives FDA Approval; url: https://www.pharmacytimes.com/news/first-targeted-therapy-for-metastatic-bladder-cancer-receives-fda-approval; parent_key: DB12147.", + "ref-id: L2323; title: Pharmacokinetic Studies on Propiverine Hydrochloride; url: https://www.jstage.jst.go.jp/article/dmpk1986/10/2/10_2_205/_article; parent_key: DB12278.", + "ref-id: L1845; title: NTP Toxicology and Carcinogenesis Studies of Polysorbate 80 (CAS No. 9005-65-6) in F344/N Rats and B6C3F1 Mice (Feed Studies).; url: https://www.ncbi.nlm.nih.gov/pubmed/12616296; parent_key: DB11063.", + "ref-id: L1570; title: Chapter 10. Vitamin K; url: http://www.fao.org/docrep/004/y2809e/y2809e0g.htm; parent_key: DB09332." + ] + }, + { + "example_idx": 75, + "anchor_id": 13916280951427504176, + "positive_id": 9942459604381226290, + "join_paths": [ + [ + 3, + 20, + 0.345703125 + ], + [ + 8, + 1, + 0.3359375 + ], + [ + 6, + 1, + 0.326171875 + ], + [ + 3, + 28, + 0.314453125 + ], + [ + 8, + 37, + 0.310546875 + ] + ], + "rows": [ + "Because estrogen contributes to the promotion and progression of breast cancer, a greater understanding of the role of estrogen in breast cancer has led to therapeutic strategies targeting estrogen synthesis, the estrogen receptor, and intracellular signaling pathways.", + "The enzyme aromatase catalyses the final step in estrogen biosynthesis and was identified as an attractive target for selective inhibition.", + "Modern third-generation aromatase inhibitors (AIs) effectively block the production of estrogen without exerting effects on other steroidogenic pathways.", + "The discovery of letrozole (Femara) achieved the goal of discovering a highly potent and totally selective AI.", + "Letrozole has greater potency than other AIs, including anastrozole, exemestane, formestane, and aminoglutethimide.", + "Moreover, letrozole produces near complete inhibition of aromatase in peripheral tissues and is associated with greater suppression of estrogen than is achieved with other AIs.", + "The potent anti-tumor effects of letrozole were demonstrated in several animal models.", + "Studies with MCF-7Ca xenografts successfully predicted that letrozole would be clinically superior to the previous gold standard tamoxifen and also indicated that it may be more effective than other AIs.", + "An extensive program of randomized clinical trials has demonstrated the clinical benefits of letrozole across the spectrum of hormone-responsive breast cancer in postmenopausal women.", + "Aged\nAnimals\nAntineoplastic Agents, Hormonal\nAromatase Inhibitors\nBreast Neoplasms\nChemotherapy, Adjuvant\nDose-Response Relationship, Drug\nFemale\nHumans\nLetrozole\nMiddle Aged\nMolecular Structure\nNeoadjuvant Therapy\nNeoplasms, Hormone-Dependent\nNitriles\nReceptors, Estrogen\nStructure-Activity Relationship\nTamoxifen\nTreatment Outcome\nTriazoles" + ], + "sentences": [ + "name: Gd-exemestane; ingredients: Exemestane; parent_key: DB00990.", + "name: Letrozole; ingredients: Letrozole; parent_key: DB01006.", + "name: Ipg-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Mylan-exemestane; ingredients: Exemestane; parent_key: DB00990.", + "name: Cytadren Tab 250mg; ingredients: Aminoglutethimide; parent_key: DB00357.", + "name: PainAway with natural peppermint and Balsam Peru; ingredients: Balsam of Peru + Levomenthol; parent_key: DB11482.", + "name: Taro-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Exemestane; ingredients: Exemestane; parent_key: DB00990.", + "name: Dom-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB01222.", + "name: Teva-exemestane; ingredients: Exemestane; parent_key: DB00990.", + "name: Cytadren; ingredients: Aminoglutethimide; parent_key: DB00357.", + "name: Menveo; ingredients: Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine + Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13889.", + "name: Arimidex; ingredients: Anastrozole; parent_key: DB01217.", + "name: Van-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Granulex; ingredients: Balsam of Peru + Castor oil + Trypsin; parent_key: DB11482.", + "name: Ran-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Arimidex Tab 1mg; ingredients: Anastrozole; parent_key: DB01217.", + "name: Act Exemestane; ingredients: Exemestane; parent_key: DB00990.", + "name: Feiba; ingredients: Anti-inhibitor coagulant complex; parent_key: DB13151.", + "name: Femara; ingredients: Letrozole; parent_key: DB01006.", + "name: Aromasin; ingredients: Exemestane; parent_key: DB00990.", + "name: Med-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Mylan-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Med-exemestane; ingredients: Exemestane; parent_key: DB00990.", + "name: Apo-exemestane; ingredients: Exemestane; parent_key: DB00990.", + "name: Anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14141.", + "name: Femara 2.5mg; ingredients: Letrozole; parent_key: DB01006.", + "name: PMS-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Apo-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Teva-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Zinda-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Mar-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Nat-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Repronex; ingredients: Follitropin + Luteinizing hormone; parent_key: DB14741.", + "name: Riva-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Letrozole Tablets; ingredients: Letrozole; parent_key: DB01006.", + "name: Atopic Healer Synergy; ingredients: Balsam of Peru + Cocoa butter; parent_key: DB11086.", + "name: Bio-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Sandoz Anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Mint-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Medi SM 24K Gold Hydrogel Peptide Mask Pack; ingredients: Adenosine + Butylene glycol + Chlorphenesin + Chondrus crispus + Glycerin + Glycyrrhiza glabra + Gold + Nicotinamide + Polysorbate 20 + Polysorbate 60 + Potassium chloride + Propolis wax + Titanium dioxide + Xanthan gum; parent_key: DB00761.", + "name: Lentaron; ingredients: Formestane + Sodium chloride; parent_key: DB08905.", + "name: Ach-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Lentaron; ingredients: Formestane + Sodium chloride; parent_key: DB09153.", + "name: Ccp-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Auro-anastrozole; ingredients: Anastrozole; parent_key: DB01217.", + "name: Accel-anastrozole Tablets; ingredients: Anastrozole; parent_key: DB01217.", + "name: Jamp-anastrozole; ingredients: Anastrozole; parent_key: DB01217." + ] + }, + { + "example_idx": 76, + "anchor_id": 11235246036671448394, + "positive_id": 7703567356411474629, + "join_paths": [ + [ + 0, + 43, + 0.251953125 + ], + [ + 0, + 35, + 0.25 + ], + [ + 2, + 35, + 0.25 + ], + [ + 0, + 2, + 0.2412109375 + ], + [ + 2, + 29, + 0.2412109375 + ] + ], + "rows": [ + "Varenicline is predominantly eliminated unchanged in urine, and active tubular secretion partially contributes to its renal elimination.", + "Transporter inhibition assays using human embryonic kidney 293 cells transfected with human renal transporters demonstrated that high concentrations of varenicline inhibited substrate uptake by hOCT2 (IC(50)=890 microM), with very weak or no measurable interactions with the other transporters hOAT1, hOAT3, hOCTN1, and hOCTN2.", + "Varenicline was characterized as a moderate-affinity substrate for hOCT2 (K(m)=370 microM) and its hOCT2-mediated uptake was partially inhibited by cimetidine.", + "Co-administration of cimetidine (1,200 mg/day) reduced the renal clearance of varenicline in 12 smokers, resulting in a 29.0% (90% CI: 21.5%-36.9%) increase in systemic exposure.", + "This increase is not considered clinically relevant, as it should not give rise to safety concerns.", + "Consequently, it can be reasonably expected that other inhibitors of hOCT2 would not cause greater renal interactions with varenicline than that seen with the efficient hOCT2 inhibitor cimetidine.", + "Adult\nBenzazepines\nChromatography, High Pressure Liquid\nCimetidine\nEmbryo, Mammalian\nEnzyme Inhibitors\nFemale\nHumans\nKidney\nMale\nMiddle Aged\nOrganic Cation Transport Proteins\nOrganic Cation Transporter 1\nOrganic Cation Transporter 2\nQuinoxalines\nReceptors, Nicotinic\nSmoking\nSmoking Cessation\nTandem Mass Spectrometry\nVarenicline" + ], + "sentences": [ + "name: Leader Heartburn Relief; ingredients: Cimetidine; parent_key: DB00501.", + "name: Ytracis; ingredients: Yttrium Y-90; parent_key: DB13076.", + "name: Gd-varenicline; ingredients: Varenicline; parent_key: DB01273.", + "name: Equaline Acid Reducer; ingredients: Cimetidine; parent_key: DB00501.", + "name: Cimetidine in Sodium Chloride; ingredients: Cimetidine; parent_key: DB00501.", + "name: Champix; ingredients: Varenicline + Varenicline; parent_key: DB01273.", + "name: Orajel 4X Medicated For Toothache and Gum; ingredients: Benzalkonium + Benzocaine + Levomenthol + Zinc cation; parent_key: DB01086.", + "name: Sterile Diluent for Allergenic Extract; ingredients: Albumin human + Phenol; parent_key: DB00062.", + "name: PMS-varenicline; ingredients: Varenicline; parent_key: DB01273.", + "name: NinePercent; ingredients: Sodium cation; parent_key: DB14516.", + "name: Up and Up Acid Reducer; ingredients: Cimetidine; parent_key: DB00501.", + "name: Chantix; ingredients: Varenicline + Varenicline; parent_key: DB01273.", + "name: Monoclate-P - 200-350iu/vial; ingredients: Antihemophilic factor human + Water; parent_key: DB13192.", + "name: TopCare Heartburn Relief; ingredients: Cimetidine; parent_key: DB00501.", + "name: Equate Cimetidine; ingredients: Cimetidine; parent_key: DB00501.", + "name: Tagamet 600; ingredients: Cimetidine; parent_key: DB00501.", + "name: Nu-cimet Tab 300mg; ingredients: Cimetidine; parent_key: DB00501.", + "name: HYLENEX Recombinant; ingredients: Hyaluronidase (human recombinant); parent_key: DB06205.", + "name: Humulin 50/50 Inj; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: SunMark heartburn relief acid reducer; ingredients: Cimetidine; parent_key: DB00501.", + "name: Harris Teeter Acid Reducer; ingredients: Cimetidine; parent_key: DB00501.", + "name: Acid Reducer; ingredients: Cimetidine; parent_key: DB00501.", + "name: Chi-Myst Synergy Topical; ingredients: Bupivacaine + Chitosan low molecular weight (20-200 mpa.s) + Ketorolac + Lidocaine; parent_key: DB14155.", + "name: Smart Sense Acid Reducer; ingredients: Cimetidine; parent_key: DB00501.", + "name: Good Neighbor Pharmacy Heartburn Relief; ingredients: Cimetidine; parent_key: DB00501.", + "name: Tagamet 300; ingredients: Cimetidine; parent_key: DB00501.", + "name: Nu-cimet Tab 200mg; ingredients: Cimetidine; parent_key: DB00501.", + "name: Gd-varenicline; ingredients: Varenicline + Varenicline; parent_key: DB01273.", + "name: Menveo; ingredients: Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine + Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13889.", + "name: Apo-varenicline; ingredients: Varenicline + Varenicline; parent_key: DB01273.", + "name: Nu-cimet Tab 600mg; ingredients: Cimetidine; parent_key: DB00501.", + "name: Heartburn Relief; ingredients: Cimetidine; parent_key: DB00501.", + "name: Cimetidine Acid Reducer; ingredients: Cimetidine; parent_key: DB00501.", + "name: Cimetidine Hydrochloride; ingredients: Cimetidine; parent_key: DB00501.", + "name: Tagamet HB; ingredients: Cimetidine; parent_key: DB00501.", + "name: Apo-varenicline; ingredients: Varenicline; parent_key: DB01273.", + "name: Teva-varenicline; ingredients: Varenicline + Varenicline; parent_key: DB01273.", + "name: Chantix; ingredients: Varenicline; parent_key: DB01273.", + "name: Nu-cimet Tab 400mg; ingredients: Cimetidine; parent_key: DB00501.", + "name: Cimetidine Hydrochloride Oral Solution; ingredients: Cimetidine; parent_key: DB00501.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB13960.", + "name: Medical Provider Single Use EZ Flu Shot Flucelvax 2014-2015 Kit; ingredients: Influenza A virus A/Brisbane/10/2010 (H1N1) antigen (MDCK cell derived, propiolactone inactivated) + Influenza A virus A/Texas/50/2012 X-223A (H3N2) antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Massachusetts/2/2012 antigen (MDCK cell derived, propiolactone inactivated); parent_key: DB10999.", + "name: Cimetidine; ingredients: Cimetidine; parent_key: DB00501.", + "name: Teva-varenicline; ingredients: Varenicline; parent_key: DB01273.", + "name: PMS-varenicline; ingredients: Varenicline + Varenicline; parent_key: DB01273.", + "name: Good Sense Heartburn Relief; ingredients: Cimetidine; parent_key: DB00501.", + "name: Tagamet; ingredients: Cimetidine; parent_key: DB00501.", + "name: Champix; ingredients: Varenicline; parent_key: DB01273.", + "name: DG Health Heartburn Relief; ingredients: Cimetidine; parent_key: DB00501.", + "name: RiaSTAP; ingredients: Fibrinogen human; parent_key: DB09222." + ] + }, + { + "example_idx": 77, + "anchor_id": 6050145551740047703, + "positive_id": 16919780008487888596, + "join_paths": [ + [ + 3, + 45, + 0.1953125 + ], + [ + 5, + 45, + 0.1591796875 + ] + ], + "rows": [ + "Probenecid is a well-established drug for the treatment of gout and is thought to act on an organic anion transporter, thereby affecting uric acid excretion in the kidney by blocking urate reuptake.", + "Probenecid also has been shown to affect ATP release, leading to the suggestion that ATP release involves an organic anion transporter.", + "Other pharmacological evidence and the observation of dye uptake, however, suggest that the nonvesicular release of ATP is mediated by large membrane channels, with pannexin 1 being a prominent candidate.", + "In the present study we show that probenecid inhibited currents mediated by pannexin 1 channels in the same concentration range as observed for inhibition of transport processes.", + "Probenecid did not affect channels formed by connexins.", + "Thus probenecid allows for discrimination between channels formed by connexins and pannexins.", + "Adenosine Triphosphate\nAnimals\nConnexins\nDose-Response Relationship, Drug\nGout Suppressants\nIon Channels\nMembrane Potentials\nNitrobenzoates\nOocytes\nProbenecid\nXenopus laevis" + ], + "sentences": [ + "id: BE0009014; name: ATP synthase subunit a; organism: Humans; known_action: unknown; position: 34; parent_key: DB13955.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 29; parent_key: DB00408.", + "id: BE0005788; name: G-protein coupled bile acid receptor 1; organism: Humans; known_action: unknown; position: 11; parent_key: DB03619.", + "id: BE0009014; name: ATP synthase subunit a; organism: Humans; known_action: unknown; position: 34; parent_key: DB13954.", + "id: BE0000013; name: Adenosine receptor A1; organism: Humans; known_action: yes; position: 3; parent_key: DB00201.", + "id: BE0001069; name: Canalicular multispecific organic anion transporter 1; organism: Humans; known_action: yes; parent_key: DB01138.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 2; parent_key: DB01211.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 7; parent_key: DB01241.", + "id: BE0001640; name: Phospholipase A2, membrane associated; organism: Humans; known_action: unknown; parent_key: DB04112.", + "id: BE0009097; name: ATP synthase subunit O, mitochondrial; organism: Humans; known_action: unknown; position: 6; parent_key: DB11638.", + "id: BE0001290; name: Response regulator PleD; organism: Caulobacter crescentus (strain ATCC 19089 / CB15); known_action: unknown; parent_key: DB01972.", + "id: BE0009014; name: ATP synthase subunit a; organism: Humans; known_action: unknown; position: 34; parent_key: DB13953.", + "id: BE0002514; name: Release factor glutamine methyltransferase; organism: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099); known_action: unknown; parent_key: DB01752.", + "id: BE0004851; name: Schistosome calcium ion (Ca2+) channels; organism: Schistosoma; known_action: yes; position: 1; parent_key: DB01058.", + "id: BE0000381; name: Gamma-aminobutyric acid receptor subunit alpha-2; organism: Humans; known_action: yes; position: 2; parent_key: DB01354.", + "id: BE0003659; name: Solute carrier organic anion transporter family member 1B3; organism: Humans; known_action: unknown; position: 15; parent_key: DB01241.", + "id: BE0000471; name: Gamma-aminobutyric acid receptor subunit alpha-5; organism: Humans; known_action: yes; position: 4; parent_key: DB01198.", + "id: BE0004823; name: Uric acid; organism: Humans; known_action: yes; position: 1; parent_key: DB09208.", + "id: BE0003659; name: Solute carrier organic anion transporter family member 1B3; organism: Humans; known_action: unknown; position: 1; parent_key: DB06749.", + "id: BE0002514; name: Release factor glutamine methyltransferase; organism: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099); known_action: unknown; parent_key: DB03473.", + "id: BE0001042; name: Solute carrier organic anion transporter family member 2B1; organism: Humans; known_action: unknown; position: 14; parent_key: DB01241.", + "id: BE0009014; name: ATP synthase subunit a; organism: Humans; known_action: unknown; position: 34; parent_key: DB13956.", + "id: BE0004833; name: Bacterial outer membrane; organism: Bacteria; known_action: yes; parent_key: DB00080.", + "id: BE0002051; name: Release factor glutamine methyltransferase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB01752.", + "id: BE0001042; name: Solute carrier organic anion transporter family member 2B1; organism: Humans; known_action: unknown; position: 7; parent_key: DB05521.", + "id: BE0009014; name: ATP synthase subunit a; organism: Humans; known_action: unknown; position: 23; parent_key: DB00783.", + "id: BE0002833; name: Copper transport protein ATOX1; organism: Humans; known_action: unknown; parent_key: DB03127.", + "id: BE0000825; name: Glutaminase kidney isoform, mitochondrial; organism: Humans; known_action: unknown; position: 12; parent_key: DB00142.", + "id: BE0009021; name: ATP synthase subunit e, mitochondrial; organism: Humans; known_action: unknown; position: 4; parent_key: DB12695.", + "id: BE0003659; name: Solute carrier organic anion transporter family member 1B3; organism: Humans; known_action: unknown; position: 2; parent_key: DB01211.", + "id: BE0004879; name: alpha1-acid glycoprotein; organism: Humans; known_action: unknown; position: 19; parent_key: DB00477.", + "id: BE0009022; name: ATP synthase subunit g, mitochondrial; organism: Humans; known_action: unknown; position: 5; parent_key: DB11638.", + "id: BE0009847; name: Voltage-gated Potassium Channels; known_action: unknown; position: 17; parent_key: DB01110.", + "id: BE0004748; name: ATP synthase subunit c; organism: Mycobacterium tuberculosis; known_action: yes; position: 2; parent_key: DB08903.", + "id: BE0009847; name: Voltage-gated Potassium Channels; known_action: unknown; position: 14; parent_key: DB01069.", + "id: BE0009014; name: ATP synthase subunit a; organism: Humans; known_action: unknown; position: 34; parent_key: DB13952.", + "id: BE0001069; name: Canalicular multispecific organic anion transporter 1; organism: Humans; known_action: unknown; parent_key: DB00171.", + "id: BE0003659; name: Solute carrier organic anion transporter family member 1B3; organism: Humans; known_action: unknown; position: 1; parent_key: DB06750.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 6; parent_key: DB05521.", + "id: BE0008669; name: Adenosine triphosphate (ATP); organism: Humans; known_action: yes; position: 5; parent_key: DB01133.", + "id: BE0004823; name: Uric acid; organism: Humans; known_action: yes; parent_key: DB00049.", + "id: BE0000708; name: ATP-sensitive inward rectifier potassium channel 11; organism: Humans; known_action: yes; position: 1; parent_key: DB01119.", + "id: BE0004448; name: Eukaryotic peptide chain release factor GTP-binding subunit ERF3A; organism: Humans; known_action: unknown; parent_key: DB04315.", + "id: BE0009022; name: ATP synthase subunit g, mitochondrial; organism: Humans; known_action: unknown; position: 5; parent_key: DB12695.", + "id: BE0004702; name: Hyaluronan mediated motility receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB08818.", + "id: BE0003719; name: Pannexin-1; organism: Humans; known_action: unknown; position: 4; parent_key: DB01032.", + "id: BE0004828; name: Adenosine; organism: Humans; known_action: yes; parent_key: DB00061.", + "id: BE0002030; name: ATP synthase subunit b; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03091.", + "id: BE0009847; name: Voltage-gated Potassium Channels; known_action: unknown; position: 3; parent_key: DB00228.", + "id: BE0003089; name: ATP-dependent Clp protease ATP-binding subunit ClpX; organism: Helicobacter pylori (strain ATCC 700392 / 26695); known_action: unknown; position: 1; parent_key: DB09275." + ] + }, + { + "example_idx": 78, + "anchor_id": 9560044371560982401, + "positive_id": 8606981625336467701, + "join_paths": [ + [ + 0, + 9, + 0.1953125 + ], + [ + 8, + 9, + 0.18359375 + ], + [ + 0, + 45, + 0.166015625 + ], + [ + 9, + 9, + 0.1572265625 + ], + [ + 8, + 45, + 0.154296875 + ] + ], + "rows": [ + "Influenza A and B viruses contain proton-selective ion channels, A/M2 and BM2, respectively, and the A/M2 channel activity is inhibited by the drugs amantadine and its methyl derivative rimantadine.", + "The structure of the pore-transmembrane domain has been determined by both x-ray crystallography [Stouffer et al.", + "(2008) Nature 451:596-599] and by NMR methods [Schnell and Chou (2008) Nature 451:591-595].", + "Whereas the crystal structure indicates a single amantadine molecule in the pore of the channel, the NMR data show four rimantadine molecules bound on the outside of the helices toward the cytoplasmic side of the membrane.", + "Drug binding includes interactions with residues 40-45 with a polar hydrogen bond between rimantadine and aspartic acid residue 44 (D44) that appears to be important.", + "These two distinct drug-binding sites led to two incompatible drug inhibition mechanisms.", + "We mutagenized D44 and R45 to alanine as these mutations are likely to interfere with rimantadine binding and lead to a drug insensitive channel.", + "However, the D44A channel was found to be sensitive to amantadine when measured by electrophysiological recordings in oocytes of Xenopus laevis and in mammalian cells, and when the D44 and R45 mutations were introduced into the influenza virus genome.", + "Furthermore, transplanting A/M2 pore residues 24-36 into BM2, yielded a pH-activated chimeric ion channel that was partially inhibited by amantadine.", + "Thus, taken together our functional data suggest that amantadine/rimantadine binding outside of the channel pore is not the primary site associated with the pharmacological inhibition of the A/M2 ion channel.", + "Amantadine\nAnimals\nAntiviral Agents\nBinding Sites\nCell Line\nDogs\nHumans\nModels, Molecular\nMutagenesis\nPatch-Clamp Techniques\nViral Matrix Proteins\nXenopus laevis" + ], + "sentences": [ + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00940.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 2; parent_key: DB06153.", + "id: BE0004808; name: Lead; organism: Humans; known_action: yes; position: 1; parent_key: DB00566.", + "id: BE0004053; name: Elongation factor Tu GTP-binding domain-containing protein 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB03619.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00986.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 34; parent_key: DB01238.", + "id: BE0004808; name: Lead; organism: Humans; known_action: yes; position: 1; parent_key: DB00974.", + "id: BE0003699; name: Matrix metalloproteinase-24; organism: Humans; known_action: yes; position: 19; parent_key: DB00786.", + "id: BE0004768; name: Acid-sensing ion channel 3; organism: Humans; known_action: yes; position: 10; parent_key: DB08838.", + "id: BE0000678; name: Acid-sensing ion channel 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB00594.", + "id: BE0002494; name: N-acylamino acid racemase; organism: Amycolatopsis sp.; known_action: unknown; parent_key: DB02251.", + "id: BE0009847; name: Voltage-gated Potassium Channels; known_action: unknown; position: 3; parent_key: DB00228.", + "id: BE0003779; name: T-cell receptor beta-1 chain C region; organism: Humans; known_action: unknown; position: 3; parent_key: DB02740.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 12; parent_key: DB00334.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; position: 1; parent_key: DB00753.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 1; parent_key: DB00785.", + "id: BE0004586; name: Catechol O-methyltransferase domain-containing protein 1; organism: Humans; known_action: unknown; parent_key: DB03923.", + "id: BE0001195; name: Cystic fibrosis transmembrane conductance regulator; organism: Humans; known_action: unknown; position: 5; parent_key: DB00887.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 1; parent_key: DB00462.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 1; parent_key: DB00376.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; parent_key: DB00728.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 9; parent_key: DB01142.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 21; parent_key: DB01224.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 2; parent_key: DB12278.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 1; parent_key: DB04834.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00809.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 2; parent_key: DB01062.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 5; parent_key: DB00767.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 5; parent_key: DB09167.", + "id: BE0004851; name: Schistosome calcium ion (Ca2+) channels; organism: Schistosoma; known_action: yes; position: 1; parent_key: DB01058.", + "id: BE0003563; name: Voltage-dependent calcium channel subunit alpha-2/delta-3; organism: Humans; known_action: unknown; position: 2; parent_key: DB00381.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; parent_key: DB00387.", + "id: BE0004808; name: Lead; organism: Humans; known_action: yes; position: 1; parent_key: DB14600.", + "id: BE0003592; name: Gamma-aminobutyric acid receptor subunit gamma-2; organism: Humans; known_action: unknown; position: 3; parent_key: DB12458.", + "id: BE0001019; name: Mitogen-activated protein kinase 14; organism: Humans; known_action: unknown; position: 1; parent_key: DB07607.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; parent_key: DB05752.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; position: 6; parent_key: DB09089.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; parent_key: DB01231.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: no; position: 24; parent_key: DB14185.", + "id: BE0009224; name: Skeleton-binding protein 1; organism: Plasmodium falciparum (isolate 3D7); known_action: unknown; position: 143; parent_key: DB11638.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: no; position: 7; parent_key: DB01151.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 1; parent_key: DB00804.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; parent_key: DB00332.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; parent_key: DB01336.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: yes; parent_key: DB01148.", + "id: BE0000353; name: Acid-sensing ion channel 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00594.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 18; parent_key: DB00408.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: no; position: 2; parent_key: DB01226.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 3; parent_key: DB00392.", + "id: BE0000560; name: Muscarinic acetylcholine receptor M2; organism: Humans; known_action: unknown; position: 2; parent_key: DB09300." + ] + }, + { + "example_idx": 79, + "anchor_id": 14223923671966893852, + "positive_id": 7176731346525520214, + "join_paths": [ + [ + 0, + 1, + 0.279296875 + ], + [ + 0, + 44, + 0.27734375 + ], + [ + 0, + 15, + 0.275390625 + ], + [ + 0, + 30, + 0.2734375 + ], + [ + 0, + 24, + 0.271484375 + ] + ], + "rows": [ + "Spironolactone and eplerenone are widely used as mineralocorticoid antagonists.", + "Spironolactone has several nonspecific actions including inhibition of androgen receptor and steroid hormone biosynthesis.", + "While studies have shown that eplerenone does not exhibit nonspecific actions on androgen receptor, its effects on steroid hormone production have not been reported.", + "Herein, the effects of eplerenone (0.1-30 microM) and spironolactone (0.1-30 microM) on steroid production were examined in human adrenocortical H295R cells.", + "Spironolactone inhibited basal production of cortisol (91%) and aldosterone (53%).", + "Treatment of H295R cells with angiotensin II (Ang II) for 24 h increased aldosterone production by 11-fold.", + "Spironolactone inhibited Ang II stimulation of aldosterone production by 80%.", + "Addition of pregnenolone increased aldosterone (9-fold) and cortisol (3-fold) production.", + "Spironolactone inhibited pregnenolone metabolism to aldosterone (67%) and cortisol (74%).", + "The inhibitory effects of spironolactone occurred at concentrations far higher than those needed to block mineralocorticoid receptor, suggesting an action directly on the enzymes involved in steroid production.", + "In contrast, eplerenone did not inhibit basal, Ang II, forskolin, pregnenolone-stimulated cortisol, or aldosterone production.", + "Together, these data demonstrate that opposed to spironolactone, pharmacologic concentrations of eplerenone do not inhibit adrenal cell aldosterone or cortisol production.", + "Adrenal Glands\nDose-Response Relationship, Drug\nEplerenone\nHumans\nHydrocortisone\nMineralocorticoid Receptor Antagonists\nMineralocorticoids\nReceptors, Mineralocorticoid\nSpironolactone\nSteroids\nTranscriptional Activation\nTumor Cells, Cultured" + ], + "sentences": [ + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01185.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; position: 13; parent_key: DB13867.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB11901.", + "id: BE0000478; name: Gamma-aminobutyric acid receptor subunit alpha-4; organism: Humans; known_action: yes; position: 3; parent_key: DB00418.", + "id: BE0000879; name: Solute carrier family 22 member 11; organism: Humans; known_action: unknown; position: 2; parent_key: DB01212.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB14639.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB07717.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB00858.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB11219.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01420.", + "id: BE0005001; name: Steroid hormone receptor ERR2; organism: Humans; known_action: unknown; position: 3; parent_key: DB07776.", + "id: BE0000291; name: 5-hydroxytryptamine receptor 1A; organism: Humans; known_action: yes; position: 3; parent_key: DB08922.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB06713.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 16; parent_key: DB00396.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; position: 9; parent_key: DB00393.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; position: 6; parent_key: DB02901.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB01541.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB04839.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB13944.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB02998.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; parent_key: DB04630.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; position: 22; parent_key: DB00624.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB00648.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB11064.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: yes; parent_key: DB00421.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB08906.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB06718.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB09173.", + "id: BE0003722; name: Steroid hormone receptor ERR1; organism: Humans; known_action: unknown; position: 2; parent_key: DB06732.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; parent_key: DB01347.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01395.", + "id: BE0000533; name: 5-hydroxytryptamine receptor 2C; organism: Humans; known_action: yes; position: 4; parent_key: DB01242.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB06412.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB07423.", + "id: BE0000389; name: Dopamine D4 receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB00409.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; parent_key: DB04652.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB11447.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB00588.", + "id: BE0000748; name: Fibroblast growth factor receptor 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB15685.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 14; parent_key: DB00655.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB13951.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 12; parent_key: DB00255.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 2; parent_key: DB13437.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: yes; parent_key: DB00621.", + "id: BE0000668; name: Mineralocorticoid receptor; organism: Humans; known_action: unknown; position: 25; parent_key: DB13944.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB07769.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB13919.", + "id: BE0000132; name: Androgen receptor; organism: Humans; known_action: unknown; position: 6; parent_key: DB02266.", + "id: BE0000797; name: 5-hydroxytryptamine receptor 1B; organism: Humans; known_action: unknown; parent_key: DB06096.", + "id: BE0000078; name: Retinoic acid receptor RXR-beta; organism: Humans; known_action: unknown; position: 3; parent_key: DB07080." + ] + }, + { + "example_idx": 81, + "anchor_id": 8638734427857635010, + "positive_id": 46405294679901371, + "join_paths": [ + [ + 7, + 3, + 0.240234375 + ], + [ + 7, + 38, + 0.2373046875 + ], + [ + 7, + 17, + 0.2275390625 + ], + [ + 7, + 12, + 0.2216796875 + ], + [ + 7, + 47, + 0.2216796875 + ] + ], + "rows": [ + "Thiazide and high ceiling diuretics were recently shown to inhibit all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1) with a very different profile as compared to classical inhibitors, such as acetazolamide, methazolamide, and ethoxzolamide.", + "Some of these structurally related compounds have a very different behavior against the widespread isozyme CA II, with chlorthalidone, trichloromethiazide, and furosemide being efficient inhibitors against CA II (K(I)s of 65-138 nM), whereas indapamide is a much weaker one (K(I) of 2520 nM).", + "Furthermore, some of these diuretics are quite efficient (low nanomolar) inhibitors of other isoforms, for example, chlorthalidone against hCA VB, VII, IX, and XIII; indapamide against CA VII, IX, XII, and XIII, trichloromethiazide against CA VII and IX, and furosemide against CA I and XIV.", + "Examining the four X-ray crystal structures of their CA II adducts, we observed several (2-3) active site water molecules interacting with the chlorthalidone, trichloromethiazide, and furosemide scaffolds which may be responsible for this important difference of activity.", + "Indeed, indapamide bound to CA II has no interactions with active site water molecules.", + "Chlorthalidone bound within the CA II active site is in an enolic (lactimic) tautomeric form, with the enolic OH also participating in two strong hydrogen bonds with Asn67 and a water molecule.", + "The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications.", + "Carbonic Anhydrase II\nCarbonic Anhydrase Inhibitors\nChlorthalidone\nCrystallography, X-Ray\nFurosemide\nIndapamide\nIsoenzymes\nStructure-Activity Relationship\nSulfonamides\nTrichlormethiazide\nWater" + ], + "sentences": [ + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: yes; position: 1; parent_key: DB00703.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: yes; position: 2; parent_key: DB00311.", + "id: BE0000131; name: Corticosteroid 11-beta-dehydrogenase isozyme 2; organism: Humans; known_action: unknown; position: 14; parent_key: DB14540.", + "id: BE0009965; name: Carbonic anhydrase; organism: Humans; known_action: yes; position: 7; parent_key: DB00562.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: yes; position: 4; parent_key: DB00273.", + "id: BE0003625; name: Carbonic anhydrase 3; organism: Humans; known_action: unknown; position: 5; parent_key: DB00311.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB00562.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: no; position: 1; parent_key: DB00423.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 117; parent_key: DB01593.", + "id: BE0003625; name: Carbonic anhydrase 3; organism: Humans; known_action: unknown; position: 3; parent_key: DB00580.", + "id: BE0003629; name: Carbonic anhydrase 7; organism: Humans; known_action: yes; position: 2; parent_key: DB00703.", + "id: BE0003625; name: Carbonic anhydrase 3; organism: Humans; known_action: unknown; position: 2; parent_key: DB00703.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00562.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB00232.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: unknown; position: 4; parent_key: DB00562.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: yes; position: 2; parent_key: DB00703.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00232.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: yes; parent_key: DB00311.", + "id: BE0002437; name: Carbonic anhydrase 9; organism: Humans; known_action: unknown; position: 5; parent_key: DB00562.", + "id: BE0003629; name: Carbonic anhydrase 7; organism: Humans; known_action: unknown; position: 1; parent_key: DB00774.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: unknown; position: 5; parent_key: DB00436.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB00381.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB00436.", + "id: BE0003625; name: Carbonic anhydrase 3; organism: Humans; known_action: unknown; position: 4; parent_key: DB00391.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB00482.", + "id: BE0009447; name: Homeodomain-interacting protein kinase 2; organism: Humans; known_action: unknown; position: 149; parent_key: DB12010.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: yes; position: 5; parent_key: DB00273.", + "id: BE0003625; name: Carbonic anhydrase 3; organism: Humans; known_action: unknown; position: 4; parent_key: DB00482.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB03385.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB00391.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: yes; position: 2; parent_key: DB00819.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: yes; position: 3; parent_key: DB00311.", + "id: BE0003629; name: Carbonic anhydrase 7; organism: Humans; known_action: yes; position: 4; parent_key: DB00311.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: unknown; position: 4; parent_key: DB00232.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00580.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB00606.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB00436.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: yes; position: 2; parent_key: DB00310.", + "id: BE0009965; name: Carbonic anhydrase; organism: Humans; known_action: yes; position: 5; parent_key: DB00606.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: no; position: 9; parent_key: DB00695.", + "id: BE0002097; name: Low affinity immunoglobulin gamma Fc region receptor III-A; organism: Humans; known_action: unknown; position: 6; parent_key: DB11767.", + "id: BE0001209; name: Casein kinase II subunit alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB04721.", + "id: BE0009088; name: Keratin, type II cytoskeletal 6A; organism: Humans; known_action: unknown; position: 104; parent_key: DB01593.", + "id: BE0003625; name: Carbonic anhydrase 3; organism: Humans; known_action: unknown; position: 8; parent_key: DB00273.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: yes; position: 2; parent_key: DB00703.", + "id: BE0002437; name: Carbonic anhydrase 9; organism: Humans; known_action: unknown; position: 2; parent_key: DB00774.", + "id: BE0001039; name: High affinity nerve growth factor receptor; organism: Humans; known_action: unknown; position: 7; parent_key: DB00321.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00606.", + "id: BE0009070; name: C4b-binding protein beta chain; organism: Humans; known_action: unknown; position: 51; parent_key: DB14548.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00273." + ] + }, + { + "example_idx": 82, + "anchor_id": 8171922276292415580, + "positive_id": 12991821693038828790, + "join_paths": [ + [ + 13, + 18, + 0.255859375 + ], + [ + 13, + 30, + 0.251953125 + ], + [ + 0, + 18, + 0.166015625 + ], + [ + 0, + 30, + 0.1640625 + ] + ], + "rows": [ + "Angiotensin type 1 receptor blockers are widely used for the treatment of hypertension, and one angiotensin type 1 receptor blocker, telmisartan, specifically activates the peroxisome proliferator-activated receptor (PPAR)-gamma.", + "We studied the impact of PPARgamma mutants on transcriptional control and interaction with cofactors to elucidate differences in the molecular mechanism between telmisartan and other PPARgamma agonists, thiazolidinediones (TZDs).", + "We created several amino acid substitutions in the ligand binding domain of PPARgamma that, based on molecular modeling, may affect the binding of these agents.", + "In transient expression experiments, wild-type PPARgamma-mediated transcription stimulated by telmisartan was more than one third of that stimulated by TZDs.", + "The activation stimulated by TZDs was impaired, whereas activation stimulated by telmisartan was retained, in the H323Y, S342A, and H449A mutants.", + "In the Y473A mutant, the TZD-induced activation was further impaired and lower than that of telmisartan-induced activation.", + "Coexpression of coactivators enhanced the activation by both telmisartan and TZDs, but activation by telmisartan always exceeded that of TZDs in the Y473A mutant.", + "Based on a mammalian two-hybrid assay, the interaction with corepressors was retained in Y473A.", + "Telmisartan and TZDs, but not 9cis retinoic acid, dissociated corepressors from the wild-type PPARgamma.", + "Telmisartan most effectively dissociated corepressors from Y473A.", + "The interaction with coactivators was enhanced by TZD activation of wild-type PPARgamma and both telmisartan and TZD activation of Y473A.", + "Thus, the Y473A mutant is selectively stimulated by telmisartan but not TZDs, suggesting that telmisartan and TZDs have differential effects on the transcriptional control.", + "In conclusion, these PPARgamma mutants could be powerful tools for developing novel therapeutic agents that retain the metabolic efficacy of PPARgamma activation with fewer adverse effects, such as the increase in body weight associated with TZDs.", + "Angiotensin II Type 1 Receptor Blockers\nBenzimidazoles\nBenzoates\nCells, Cultured\nHormone Antagonists\nHumans\nModels, Biological\nMutant Proteins\nPPAR alpha\nPPAR delta\nPPAR gamma\nProtein Binding\nRetinoid X Receptors\nSubstrate Specificity\nTelmisartan\nThiazolidinediones\nTranscriptional Activation\nTransfection" + ], + "sentences": [ + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; parent_key: DB11811.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; parent_key: DB05187.", + "id: BE0000915; name: Hepatocyte growth factor receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB06995.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 5; parent_key: DB02746.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB13873.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB00573.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB09422.", + "id: BE0009583; name: 5-hydroxytryptamine receptor 3B; organism: Humans; known_action: unknown; position: 15; parent_key: DB00988.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: yes; parent_key: DB00197.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: yes; parent_key: DB04942.", + "id: BE0002098; name: Low affinity immunoglobulin gamma Fc region receptor II-a; organism: Humans; known_action: unknown; position: 3; parent_key: DB00054.", + "id: BE0004545; name: Nuclear receptor ROR-alpha; organism: Humans; known_action: unknown; parent_key: DB01990.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 16; parent_key: DB03017.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; parent_key: DB05854.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 4; parent_key: DB00132.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 49; parent_key: DB08231.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 5; parent_key: DB01708.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; parent_key: DB00799.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; parent_key: DB01029.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB01252.", + "id: BE0009451; name: Insulin receptor-related protein; organism: Humans; known_action: unknown; position: 155; parent_key: DB12010.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: unknown; parent_key: DB02258.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: yes; position: 3; parent_key: DB01393.", + "id: BE0000663; name: Retinoic acid receptor alpha; organism: Humans; known_action: unknown; parent_key: DB00982.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 23; parent_key: DB02709.", + "id: BE0001443; name: Aliphatic amidase expression-regulating protein; organism: Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228); known_action: unknown; parent_key: DB02736.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB08402.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 7; parent_key: DB02266.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; parent_key: DB06521.", + "id: BE0000405; name: Muscarinic acetylcholine receptor M4; organism: Humans; known_action: yes; position: 5; parent_key: DB01036.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; parent_key: DB00796.", + "id: BE0000663; name: Retinoic acid receptor alpha; organism: Humans; known_action: unknown; parent_key: DB05785.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: unknown; parent_key: DB03466.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: yes; position: 3; parent_key: DB00459.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; position: 4; parent_key: DB00459.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB00845.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 2; parent_key: DB07863.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB08302.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB07215.", + "id: BE0001209; name: Casein kinase II subunit alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB04719.", + "id: BE0000623; name: Tyrosine-protein phosphatase non-receptor type 1; organism: Humans; known_action: unknown; parent_key: DB02977.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB07111.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 21; parent_key: DB14011.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 7; parent_key: DB02746.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 5; parent_key: DB00328.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: yes; position: 1; parent_key: DB01014.", + "id: BE0000099; name: Cysteinyl leukotriene receptor 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB08855.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: yes; position: 1; parent_key: DB11133.", + "id: BE0000663; name: Retinoic acid receptor alpha; organism: Humans; known_action: unknown; position: 8; parent_key: DB00210.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB07208." + ] + }, + { + "example_idx": 83, + "anchor_id": 8837693798513443821, + "positive_id": 1405953997558842230, + "join_paths": [ + [ + 5, + 35, + 0.361328125 + ], + [ + 4, + 35, + 0.333984375 + ], + [ + 6, + 35, + 0.318359375 + ], + [ + 3, + 35, + 0.296875 + ], + [ + 2, + 35, + 0.2890625 + ] + ], + "rows": [ + "Chronic hepatitis B is a worldwide health problem.", + "Research interests have focused on the development of potent and safe antiviral agents with low resistance rates.", + "Among these, telbivudine is an oral nucleoside analogue with specific activity against hepatitis B virus DNA polymerase.", + "Various prospective, randomized clinical trials have demonstrated the potent efficacy of telbivudine in suppressing viral replication and achieving hepatitis B e antigen seroconversion.", + "Telbivudine was also proved to be superior to lamivudine and adefovir dipivoxil.", + "This article provides an overview of the pharmacokinetics, clinical efficacies, resistance profile and safety of telbivudine.", + "A comparison of telbivudine with other oral antiviral agents is also highlighted.", + "Antiviral Agents\nClinical Trials as Topic\nDrug Resistance, Viral\nHepatitis B virus\nHepatitis B, Chronic\nHumans\nNucleic Acid Synthesis Inhibitors\nNucleosides\nPyrimidinones\nTelbivudine\nThymidine\nVirus Replication" + ], + "sentences": [ + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Patent Blue which could result in a higher serum level.; parent_key: DB13967.", + "drugbank-id: DB10989; name: Hepatitis A Vaccine; description: The therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Eculizumab.; parent_key: DB01257.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: The risk or severity of nephrotoxicity can be increased when Adefovir dipivoxil is combined with Nitroaspirin.; parent_key: DB12445.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Synthetic Conjugated Estrogens, B which could result in a higher serum level.; parent_key: DB09318.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Glipizide which could result in a higher serum level.; parent_key: DB01067.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Moxisylyte which could result in a higher serum level.; parent_key: DB09205.", + "drugbank-id: DB01416; name: Cefpodoxime; description: The risk or severity of nephrotoxicity and hypocalcemia can be increased when Cefpodoxime is combined with Pamidronic acid.; parent_key: DB00282.", + "drugbank-id: DB10989; name: Hepatitis A Vaccine; description: The therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Floxuridine.; parent_key: DB00322.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: The risk or severity of nephrotoxicity can be increased when Adefovir dipivoxil is combined with Zaltoprofen.; parent_key: DB06737.", + "drugbank-id: DB00709; name: Lamivudine; description: The serum concentration of Lamivudine can be increased when it is combined with Trimethoprim.; parent_key: DB00440.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Sumatriptan which could result in a higher serum level.; parent_key: DB00669.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Inositol which could result in a higher serum level.; parent_key: DB13178.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Ribavirin which could result in a higher serum level.; parent_key: DB00811.", + "drugbank-id: DB00709; name: Lamivudine; description: Saquinavir may decrease the excretion rate of Lamivudine which could result in a higher serum level.; parent_key: DB01232.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Bekanamycin which could result in a higher serum level.; parent_key: DB13673.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: The risk or severity of nephrotoxicity can be increased when Adefovir dipivoxil is combined with Acetylsalicylic acid.; parent_key: DB00945.", + "drugbank-id: DB11148; name: Butamben; description: Hyaluronidase (ovine) can cause an increase in the absorption of Butamben resulting in an increased serum concentration and potentially a worsening of adverse effects.; parent_key: DB00070.", + "drugbank-id: DB11627; name: Hepatitis B Vaccine (Recombinant); description: The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Siltuximab.; parent_key: DB09036.", + "drugbank-id: DB00709; name: Lamivudine; description: Prednisone may decrease the excretion rate of Lamivudine which could result in a higher serum level.; parent_key: DB00635.", + "drugbank-id: DB10343; name: Bacillus calmette-guerin substrain tice live antigen; description: The therapeutic efficacy of Fluocinolone acetonide can be decreased when used in combination with Bacillus calmette-guerin substrain tice live antigen.; parent_key: DB00591.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Mangafodipir which could result in a higher serum level.; parent_key: DB06796.", + "drugbank-id: DB00709; name: Lamivudine; description: The serum concentration of Lamivudine can be increased when it is combined with Chlorpheniramine.; parent_key: DB01114.", + "drugbank-id: DB00709; name: Lamivudine; description: Methotrexate may decrease the excretion rate of Lamivudine which could result in a higher serum level.; parent_key: DB00563.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: The risk or severity of nephrotoxicity can be increased when Adefovir dipivoxil is combined with Antrafenine.; parent_key: DB01419.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Auranofin which could result in a higher serum level.; parent_key: DB00995.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Chromium nicotinate which could result in a higher serum level.; parent_key: DB14529.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Testosterone which could result in a higher serum level.; parent_key: DB00624.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Hydroxyethyl Starch which could result in a higher serum level.; parent_key: DB09106.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: The excretion of Captopril can be decreased when combined with Adefovir dipivoxil.; parent_key: DB01197.", + "drugbank-id: DB14596; name: Loteprednol etabonate; description: The therapeutic efficacy of Rabies virus inactivated antigen, B can be decreased when used in combination with Loteprednol etabonate.; parent_key: DB10062.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: The risk or severity of nephrotoxicity can be increased when Adefovir dipivoxil is combined with Pirprofen.; parent_key: DB13722.", + "drugbank-id: DB12598; name: Nafamostat; description: The risk or severity of bleeding can be increased when Nafamostat is combined with Alteplase.; parent_key: DB00009.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Technetium Tc-99m mebrofenin which could result in a higher serum level.; parent_key: DB09137.", + "drugbank-id: DB01250; name: Olsalazine; description: Olsalazine may decrease the excretion rate of Folic acid which could result in a higher serum level.; parent_key: DB00158.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Hydralazine which could result in a higher serum level.; parent_key: DB01275.", + "drugbank-id: DB01265; name: Telbivudine; description: The therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Telbivudine.; parent_key: DB11003.", + "drugbank-id: DB05109; name: Trabectedin; description: The therapeutic efficacy of Vaccinia virus strain new york city board of health live antigen can be decreased when used in combination with Trabectedin.; parent_key: DB14711.", + "drugbank-id: DB00709; name: Lamivudine; description: The serum concentration of Lamivudine can be increased when it is combined with Varenicline.; parent_key: DB01273.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Ropivacaine which could result in a higher serum level.; parent_key: DB00296.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Ezogabine which could result in a higher serum level.; parent_key: DB04953.", + "drugbank-id: DB00709; name: Lamivudine; description: The serum concentration of Lamivudine can be increased when it is combined with Metoprolol.; parent_key: DB00264.", + "drugbank-id: DB10989; name: Hepatitis A Vaccine; description: The therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Hydroxyurea.; parent_key: DB01005.", + "drugbank-id: DB00709; name: Lamivudine; description: Firocoxib may decrease the excretion rate of Lamivudine which could result in a higher serum level.; parent_key: DB09217.", + "drugbank-id: DB10989; name: Hepatitis A Vaccine; description: The therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Temozolomide.; parent_key: DB00853.", + "drugbank-id: DB10989; name: Hepatitis A Vaccine; description: The therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Belimumab.; parent_key: DB08879.", + "drugbank-id: DB00866; name: Alprenolol; description: The risk of a hypersensitivity reaction to Poa pratensis pollen is increased when it is combined with Alprenolol.; parent_key: DB10366.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: The risk or severity of nephrotoxicity can be increased when Adefovir dipivoxil is combined with Floctafenine.; parent_key: DB08976.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Streptomycin which could result in a higher serum level.; parent_key: DB01082.", + "drugbank-id: DB13275; name: Clorindione; description: The risk or severity of bleeding can be increased when Bivalirudin is combined with Clorindione.; parent_key: DB00006.", + "drugbank-id: DB00718; name: Adefovir dipivoxil; description: Adefovir dipivoxil may decrease the excretion rate of Levocetirizine which could result in a higher serum level.; parent_key: DB06282." + ] + }, + { + "example_idx": 84, + "anchor_id": 5111814664588555428, + "positive_id": 8362249610266885284, + "join_paths": [ + [ + 4, + 6, + 0.24609375 + ], + [ + 4, + 1, + 0.2451171875 + ], + [ + 4, + 12, + 0.2392578125 + ], + [ + 4, + 49, + 0.2294921875 + ], + [ + 7, + 1, + 0.2294921875 + ] + ], + "rows": [ + "BACKGROUND: Failure of anastomotic healing is one of the major complications in colorectal surgery.", + "Because histamine plays an important role in immune and inflammatory reactions, we demonstrate the effects of famotidine on the healing of colonic anastomosis in rats.", + "METHODS: Twenty-eight Sprague-Dawley rats were used in the study.", + "Excision and end-to-end anastomosis was performed in the distal colon of the rat.", + "The Famotidine Group received 2 mg/kg/day famotidine; the Control Group received the same amount of saline.", + "Bursting pressure of anastomoses and hydroxyproline content of perianastomotic tissues were evaluated on the third and seventh days following surgery.", + "RESULTS: Bursting pressures and hydroxyproline contents for the Famotidine Group were significantly lower than the equivalent parameters for the Control Group on both the third and seventh days post-surgery.", + "CONCLUSIONS: According to our findings, famotidine exerts detrimental effects on the anastomotic bursting pressure and hydroxyproline content of perianastomotic tissues in the colon of rats.", + "Anastomosis, Surgical\nAnimals\nColon\nDisease Models, Animal\nFamotidine\nHistamine H2 Antagonists\nMale\nRats\nRats, Sprague-Dawley\nStatistics, Nonparametric\nWound Healing" + ], + "sentences": [ + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Glasdegib.; parent_key: DB11978.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Famotidine can be decreased when combined with Pantoprazole.; parent_key: DB00213.", + "drugbank-id: DB13786; name: Magnesium orotate; description: The risk or severity of adverse effects can be increased when Magnesium orotate is combined with Botulinum Toxin Type B.; parent_key: DB00042.", + "drugbank-id: DB06603; name: Panobinostat; description: The therapeutic efficacy of Human rabies virus immune globulin can be decreased when used in combination with Panobinostat.; parent_key: DB11603.", + "drugbank-id: DB14018; name: Bromotheophylline; description: Bromotheophylline may increase the excretion rate of Tenofovir disoproxil which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB00300.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Famotidine can be decreased when combined with Melatonin.; parent_key: DB01065.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Famotidine can be decreased when combined with Aminohippuric acid.; parent_key: DB00345.", + "drugbank-id: DB03450; name: Cephalothin Group; description: The risk or severity of nephrotoxicity can be increased when Hydrochlorothiazide is combined with Cephalothin Group.; parent_key: DB00999.", + "drugbank-id: DB05381; name: Histamine; description: The risk or severity of adverse effects can be increased when Dacomitinib is combined with Histamine.; parent_key: DB11963.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Escitalopram.; parent_key: DB01175.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Zuclopenthixol.; parent_key: DB01624.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Estradiol can be decreased when combined with Famotidine.; parent_key: DB00783.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Hydrochlorothiazide can be decreased when combined with Famotidine.; parent_key: DB00999.", + "drugbank-id: DB00927; name: Famotidine; description: The metabolism of Verapamil can be decreased when combined with Famotidine.; parent_key: DB00661.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Risperidone is combined with Famotidine.; parent_key: DB00734.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Citrulline can be decreased when combined with Famotidine.; parent_key: DB00155.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Losartan is combined with Famotidine.; parent_key: DB00678.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Famotidine can be decreased when combined with Cephalexin.; parent_key: DB00567.", + "drugbank-id: DB15246; name: Salvianolic acid A; description: Salvianolic acid A can cause an increase in the absorption of Raltegravir resulting in an increased serum concentration and potentially a worsening of adverse effects.; parent_key: DB06817.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Famotidine can be decreased when combined with Liotrix.; parent_key: DB01583.", + "drugbank-id: DB12104; name: Tarextumab; description: The risk or severity of adverse effects can be increased when Adalimumab is combined with Tarextumab.; parent_key: DB00051.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Ranolazine.; parent_key: DB00243.", + "drugbank-id: DB00927; name: Famotidine; description: The metabolism of Hypoxanthine can be decreased when combined with Famotidine.; parent_key: DB04076.", + "drugbank-id: DB00927; name: Famotidine; description: The therapeutic efficacy of Pazopanib can be decreased when used in combination with Famotidine.; parent_key: DB06589.", + "drugbank-id: DB00927; name: Famotidine; description: The metabolism of Rasagiline can be decreased when combined with Famotidine.; parent_key: DB01367.", + "drugbank-id: DB00927; name: Famotidine; description: The metabolism of Etamiphylline can be decreased when combined with Famotidine.; parent_key: DB13592.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Famotidine can be decreased when combined with Rucaparib.; parent_key: DB12332.", + "drugbank-id: DB05381; name: Histamine; description: The risk or severity of adverse effects can be increased when Guanfacine is combined with Histamine.; parent_key: DB01018.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Famotidine can be decreased when combined with Oxytetracycline.; parent_key: DB00595.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Lurasidone.; parent_key: DB08815.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Nicardipine is combined with Famotidine.; parent_key: DB00622.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Tacrolimus is combined with Famotidine.; parent_key: DB00864.", + "drugbank-id: DB09378; name: Fluprednisolone; description: The therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Fluprednisolone.; parent_key: DB09057.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Triptorelin.; parent_key: DB06825.", + "drugbank-id: DB00927; name: Famotidine; description: The metabolism of Hesperetin can be decreased when combined with Famotidine.; parent_key: DB01094.", + "drugbank-id: DB09027; name: Ledipasvir; description: Torasemide may increase the excretion rate of Ledipasvir which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB00214.", + "drugbank-id: DB00927; name: Famotidine; description: The metabolism of Frovatriptan can be decreased when combined with Famotidine.; parent_key: DB00998.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Promethazine.; parent_key: DB01069.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Mifepristone.; parent_key: DB00834.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Famotidine can be decreased when combined with Lansoprazole.; parent_key: DB00448.", + "drugbank-id: DB09244; name: Pirlindole; description: The risk or severity of bleeding and hemorrhage can be increased when Pirlindole is combined with Abciximab.; parent_key: DB00054.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Methotrimeprazine.; parent_key: DB01403.", + "drugbank-id: DB15076; name: Abrilumab; description: The risk or severity of adverse effects can be increased when Adalimumab is combined with Abrilumab.; parent_key: DB00051.", + "drugbank-id: DB00927; name: Famotidine; description: The metabolism of Etoposide can be decreased when combined with Famotidine.; parent_key: DB00773.", + "drugbank-id: DB11731; name: Depatuxizumab mafodotin; description: The risk or severity of adverse effects can be increased when Abciximab is combined with Depatuxizumab mafodotin.; parent_key: DB00054.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Lumefantrine.; parent_key: DB06708.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Romidepsin.; parent_key: DB06176.", + "drugbank-id: DB00927; name: Famotidine; description: The therapeutic efficacy of Hyaluronidase (ovine) can be decreased when used in combination with Famotidine.; parent_key: DB00070.", + "drugbank-id: DB00927; name: Famotidine; description: The risk or severity of QTc prolongation can be increased when Famotidine is combined with Oxatomide.; parent_key: DB12877.", + "drugbank-id: DB00927; name: Famotidine; description: The excretion of Fexofenadine can be decreased when combined with Famotidine.; parent_key: DB00950." + ] + }, + { + "example_idx": 85, + "anchor_id": 11303697264656906593, + "positive_id": 11971083405994685742, + "join_paths": [ + [ + 5, + 36, + 0.2451171875 + ], + [ + 5, + 30, + 0.244140625 + ], + [ + 5, + 2, + 0.2431640625 + ], + [ + 5, + 14, + 0.2431640625 + ], + [ + 5, + 23, + 0.2431640625 + ] + ], + "rows": [ + "Methadone (Racemic methadone) exerts its antinociceptive effect by activation of mu-opioid receptors and/or blockade of NMDA receptors.", + "The aim of this study is to determine whether the methadone analgesic effect on neuropathic pain is achieved only by the agonism of the mu-opioid receptors or cooperatively with the antagonism of the NMDA receptors.", + "To this purpose, in rats with neuropathic pain model of chronic constriction of one sciatic nerve (CCI rats), we administered methadone before or after opioid receptor blockade with naloxone and checked its effects on the spinal Wide Dynamic Range (WDR) neuron dynamics in three experimental conditions: on the spontaneous and noxious evoked neuronal activities in control rats (sham operated and naïve); on iontophoretic NMDA induced neuronal hyperactivity in intact rats; on pain-related spontaneous and noxious evoked hyperactivities in CCI rats.", + "The results, as from the spike-frequency analysis, show that: (i) in control rats, methadone inhibits the noxious evoked neuronal activity and naloxone prevents or reverses about 94% of methadone inhibitory effect; (ii) in intact rats, pretreated with naloxone, methadone reduces the NMDA induced neuronal hyperactivity; (iii) in CCI rats, methadone inhibits the neuronal spontaneous and noxious evoked hyperactivities, and naloxone prevents or reverses about 60% of methadone inhibitory effect.", + "These findings allow to conclude that methadone inhibition of the noxious evoked activity in normal rats is achieved predominantly through the agonism of the mu-opioid receptors, while the inhibition of the pain-related hyperactivity in rats with signs of neuropathic pain (CCI rats), involves also the NMDA receptors antagonism.", + "Analgesics, Opioid\nAnimals\nBehavior, Animal\nMale\nMethadone\nNeuralgia\nNeurons\nRats\nRats, Sprague-Dawley\nReceptors, N-Methyl-D-Aspartate\nReceptors, Opioid, mu\nSpine" + ], + "sentences": [ + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB01452.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00836.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01466.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00647.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB09195.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00844.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00504.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09304.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB00397.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB11273.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09194.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; parent_key: DB00217.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB06800.", + "id: BE0000945; name: 5-hydroxytryptamine receptor 6; organism: Humans; known_action: unknown; position: 20; parent_key: DB00477.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB09289.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB09173.", + "id: BE0001109; name: Ras-related C3 botulinum toxin substrate 1; organism: Humans; known_action: unknown; parent_key: DB04315.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB00956.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 26; parent_key: DB00321.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01565.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: no; position: 6; parent_key: DB00243.", + "id: BE0000812; name: Glutathione S-transferase Mu 4; organism: Humans; known_action: unknown; parent_key: DB03706.", + "id: BE0000797; name: 5-hydroxytryptamine receptor 1B; organism: Humans; known_action: yes; position: 1; parent_key: DB00216.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 17; parent_key: DB09061.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB00370.", + "id: BE0000396; name: Glutamate receptor ionotropic, NMDA 2D; organism: Humans; known_action: unknown; position: 5; parent_key: DB00454.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 2; parent_key: DB00841.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; parent_key: DB06409.", + "id: BE0000841; name: Ephrin type-A receptor 2; organism: Humans; known_action: unknown; position: 119; parent_key: DB12010.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB11130.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB00611.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB01081.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 9; parent_key: DB00715.", + "id: BE0000247; name: Muscarinic acetylcholine receptor M5; organism: Humans; known_action: unknown; position: 5; parent_key: DB00747.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB01192.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB01183.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 25; parent_key: DB14009.", + "id: BE0003872; name: Disintegrin and metalloproteinase domain-containing protein 28; organism: Humans; known_action: unknown; position: 1; parent_key: DB02215.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 14; parent_key: DB00934.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB14146.", + "id: BE0000442; name: Histamine H1 receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB11235.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00295.", + "id: BE0000826; name: Glutamate receptor ionotropic, kainate 2; organism: Humans; known_action: unknown; position: 10; parent_key: DB01174.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; parent_key: DB00697.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 39; parent_key: DB01238.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: unknown; position: 13; parent_key: DB00715.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 10; parent_key: DB09167.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB06707.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 9; parent_key: DB00490.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; parent_key: DB06230." + ] + }, + { + "example_idx": 86, + "anchor_id": 13972155892920976911, + "positive_id": 167563360308065357, + "join_paths": [ + [ + 4, + 15, + 0.1728515625 + ], + [ + 3, + 7, + 0.171875 + ], + [ + 4, + 22, + 0.171875 + ], + [ + 3, + 10, + 0.166015625 + ] + ], + "rows": [ + "The anti-alcoholism drug disulfiram (Antabuse), which is an inhibitor of aldehyde dehydrogenase, induces an aversive reaction to alcohol consumption and thereby helps patients reduce alcohol intake.", + "Recent clinical trials, initiated to investigate whether disulfiram could be used to treat individuals who abuse both alcohol and cocaine, have indicated that disulfiram effectively decreases cocaine consumption.", + "Yet the ability of disulfiram to curb cocaine intake cannot be explained by the disruption of ethanol metabolism.", + "Here, we synthesize clinical and animal data that point to dopamine beta-hydroxylase inhibition as a mechanism underlying the efficacy of disulfiram in the treatment of cocaine dependence.", + "Animals\nClinical Trials as Topic\nCocaine-Related Disorders\nDisulfiram\nDopamine beta-Hydroxylase\nEnzyme Inhibitors\nHumans\nSecondary Prevention" + ], + "sentences": [ + "id: BE0003337; name: R-specific alcohol dehydrogenase; organism: Lactobacillus brevis; known_action: unknown; parent_key: DB04784.", + "id: BE0000400; name: Alcohol dehydrogenase 1B; organism: Humans; known_action: unknown; parent_key: DB02481.", + "id: BE0001094; name: Beta-nerve growth factor; organism: Humans; known_action: unknown; position: 4; parent_key: DB01407.", + "id: BE0001415; name: Tubulin beta-3 chain; organism: Humans; known_action: unknown; parent_key: DB03010.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB01711.", + "id: BE0000244; name: Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0004352; name: Alcohol dehydrogenase [NADP(+)]; organism: Humans; known_action: unknown; position: 1; parent_key: DB02383.", + "id: BE0000138; name: Dopamine beta-hydroxylase; organism: Humans; known_action: yes; position: 1; parent_key: DB00822.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB04448.", + "id: BE0003017; name: Quinoprotein ethanol dehydrogenase; organism: Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228); known_action: unknown; parent_key: DB03205.", + "id: BE0000138; name: Dopamine beta-hydroxylase; organism: Humans; known_action: yes; position: 7; parent_key: DB00988.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB03020.", + "id: BE0000960; name: Dihydropyrimidine dehydrogenase [NADP(+)]; organism: Humans; known_action: unknown; parent_key: DB03048.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB04312.", + "id: BE0000400; name: Alcohol dehydrogenase 1B; organism: Humans; known_action: unknown; parent_key: DB04105.", + "id: BE0001413; name: Cocaine esterase; organism: Rhodococcus sp. (strain MB1 Bresler); known_action: unknown; parent_key: DB03793.", + "id: BE0001012; name: Beta-3 adrenergic receptor; organism: Humans; known_action: yes; position: 8; parent_key: DB00368.", + "id: BE0000227; name: Alcohol dehydrogenase 1A; organism: Humans; known_action: yes; position: 1; parent_key: DB01213.", + "id: BE0000400; name: Alcohol dehydrogenase 1B; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB02822.", + "id: BE0000360; name: Alcohol dehydrogenase 4; organism: Humans; known_action: unknown; parent_key: DB03559.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0001413; name: Cocaine esterase; organism: Rhodococcus sp. (strain MB1 Bresler); known_action: unknown; parent_key: DB01795.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB04071.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB03061.", + "id: BE0001870; name: Quinohemoprotein ethanol dehydrogenase type-1; organism: Comamonas testosteroni; known_action: unknown; parent_key: DB03317.", + "id: BE0000400; name: Alcohol dehydrogenase 1B; organism: Humans; known_action: yes; position: 2; parent_key: DB01213.", + "id: BE0002356; name: Voltage-dependent L-type calcium channel subunit beta-4; organism: Humans; known_action: yes; position: 8; parent_key: DB00393.", + "id: BE0000400; name: Alcohol dehydrogenase 1B; organism: Humans; known_action: unknown; parent_key: DB03461.", + "id: BE0000400; name: Alcohol dehydrogenase 1B; organism: Humans; known_action: unknown; parent_key: DB03703.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB04113.", + "id: BE0000389; name: Dopamine D4 receptor; organism: Humans; known_action: yes; position: 6; parent_key: DB01267.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; position: 1; parent_key: DB02871.", + "id: BE0000792; name: Estrogen receptor beta; organism: Humans; known_action: yes; position: 25; parent_key: DB00286.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: yes; parent_key: DB04942.", + "id: BE0000009; name: Alcohol dehydrogenase class-3; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0000009; name: Alcohol dehydrogenase class-3; organism: Humans; known_action: unknown; parent_key: DB04153.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; position: 14; parent_key: DB02659.", + "id: BE0000360; name: Alcohol dehydrogenase 4; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0001870; name: Quinohemoprotein ethanol dehydrogenase type-1; organism: Comamonas testosteroni; known_action: unknown; parent_key: DB03679.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB02721.", + "id: BE0000400; name: Alcohol dehydrogenase 1B; organism: Humans; known_action: unknown; position: 3; parent_key: DB09462.", + "id: BE0004352; name: Alcohol dehydrogenase [NADP(+)]; organism: Humans; known_action: unknown; parent_key: DB03461.", + "id: BE0000647; name: Sodium-dependent dopamine transporter; organism: Humans; known_action: unknown; position: 2; parent_key: DB01161.", + "id: BE0000009; name: Alcohol dehydrogenase class-3; organism: Humans; known_action: unknown; parent_key: DB03704.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB02757.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB03226.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: unknown; parent_key: DB02249.", + "id: BE0000465; name: Alcohol dehydrogenase 1C; organism: Humans; known_action: yes; position: 3; parent_key: DB01213.", + "id: BE0001853; name: Alcohol dehydrogenase; organism: Geobacillus stearothermophilus; known_action: unknown; parent_key: DB03226." + ] + }, + { + "example_idx": 87, + "anchor_id": 8673640192241514476, + "positive_id": 9925833375132931944, + "join_paths": [ + [ + 0, + 26, + 0.31640625 + ], + [ + 0, + 6, + 0.310546875 + ], + [ + 0, + 13, + 0.302734375 + ], + [ + 0, + 43, + 0.302734375 + ], + [ + 0, + 7, + 0.298828125 + ] + ], + "rows": [ + "The diltiazem binding site of L-type calcium channels is the least characterized to date.", + "In this paper, we present some of the available chemotypes that bind to the benzothiazepine binding site: natural compounds, compounds synthesized by varying the benzothiazepine scaffold, and compounds discovered by means of computational approaches.", + "Binding Sites\nCalcium Channel Blockers\nCalcium Channels, L-Type\nComputer Simulation\nDiltiazem\nLigands" + ], + "sentences": [ + "name: Cardizem CD; ingredients: Diltiazem; parent_key: DB00343.", + "name: Act Diltiazem CD; ingredients: Diltiazem; parent_key: DB00343.", + "name: Nu-diltiaz-CD Capsules; ingredients: Diltiazem; parent_key: DB00343.", + "name: Taro-diltiazem Tab 30mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: CyFolex; ingredients: Bovine type I collagen + Calcium carbonate + Cholecalciferol + Folic acid; parent_key: DB06724.", + "name: Gen-diltiazem SR 90mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: Diltiazem hydrochloride; ingredients: Diltiazem; parent_key: DB00343.", + "name: Diltiazem Hydrochloride Injection; ingredients: Diltiazem; parent_key: DB00343.", + "name: Diltzac; ingredients: Diltiazem; parent_key: DB00343.", + "name: Gen-diltiazem - Tab 30mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: Tiazac Xc; ingredients: Diltiazem; parent_key: DB00343.", + "name: Ipol; ingredients: Poliovirus type 1 antigen (formaldehyde inactivated) + Poliovirus type 2 antigen (formaldehyde inactivated) + Poliovirus type 3 antigen (formaldehyde inactivated); parent_key: DB10797.", + "name: Clinimix E; ingredients: Alanine + Arginine + Calcium chloride + Dextrose, unspecified form + Dipotassium phosphate + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Magnesium chloride + Methionine + Phenylalanine + Proline + Serine + Sodium acetate + Sodium chloride + Threonine + Tryptophan + Tyrosine + Valine; parent_key: DB00160.", + "name: Diltiazem Hci; ingredients: Diltiazem; parent_key: DB00343.", + "name: Gen-diltiazem SR 120mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: Teva-diltiazem Xc; ingredients: Diltiazem; parent_key: DB00343.", + "name: 4392 First Aid Kit; ingredients: Acetaminophen + Ammonia + Benzalkonium + Calcium carbonate + Ethanol + Ibuprofen + Isopropyl alcohol + Lidocaine + Neomycin + Phenylephrine + Water; parent_key: DB00994.", + "name: Ava-diltiazem; ingredients: Diltiazem; parent_key: DB00343.", + "name: Teva-diltiazem; ingredients: Diltiazem; parent_key: DB00343.", + "name: Diltiazem Hydrochloride Extended-release; ingredients: Diltiazem; parent_key: DB00343.", + "name: Diltiazem-30 Tab 30mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: Nu-diltiaz-CD Capsules 180mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: Teva-diltiazem HCl ER Capsules; ingredients: Diltiazem; parent_key: DB00343.", + "name: Prenatal Supplement - Tab; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Chromic chloride + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Ferrous fumarate + Folic acid + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Potassium Iodide + Pyridoxine + Riboflavin + Sodium molybdate + Thiamine + Vitamin A + Zinc; parent_key: DB00158.", + "name: Dilt-CD; ingredients: Diltiazem; parent_key: DB00343.", + "name: Cardizem LA; ingredients: Diltiazem; parent_key: DB00343.", + "name: Diltiazem Hydrochloride; ingredients: Diltiazem; parent_key: DB00343.", + "name: Osteo-force; ingredients: Ascorbic acid + Calcium + Cholecalciferol + Cyanocobalamin + Equisetum arvense top + Folic acid + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Potassium + Pyridoxine + Riboflavin + Thiamine + Zinc; parent_key: DB00140.", + "name: Nu-diltiaz Tab 30mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: Tiazac; ingredients: Diltiazem; parent_key: DB00343.", + "name: Acid Concentrate A1276; ingredients: Acetic acid + Calcium chloride + Dextrose, unspecified form + Magnesium chloride + Potassium chloride + Sodium chloride; parent_key: DB01164.", + "name: Multi Tabs; ingredients: Ascorbic acid + Biotin + Calcium + Cholecalciferol + Choline + Chromium + Cyanocobalamin + Folic acid + Inositol + Magnesium + Manganese + Niacin + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Thiamine + Vitamin A + Vitamin E + Zinc; parent_key: DB00165.", + "name: BOTOX Cosmetic; ingredients: Botulinum toxin type A; parent_key: DB00083.", + "name: Nuceiva; ingredients: Botulinum toxin type A; parent_key: DB00083.", + "name: Children's Chewable Vit and Min Tab; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Choline + Cyanocobalamin + Folic acid + Inositol + Iron + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Potassium + Pyridoxine + Riboflavin + Thiamine + Vitamin E + Zinc; parent_key: DB00122.", + "name: Xeomin; ingredients: Botulinum toxin type A; parent_key: DB00083.", + "name: Sandoz Diltiazem T; ingredients: Diltiazem; parent_key: DB00343.", + "name: Cardizem SR 90mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: Imovax Polio; ingredients: Poliovirus type 1 antigen (formaldehyde inactivated) + Poliovirus type 2 antigen (formaldehyde inactivated) + Poliovirus type 3 antigen (formaldehyde inactivated); parent_key: DB10797.", + "name: Apo-diltiaz SR; ingredients: Diltiazem; parent_key: DB00343.", + "name: Ipol; ingredients: Poliovirus type 1 antigen (formaldehyde inactivated) + Poliovirus type 2 antigen (formaldehyde inactivated) + Poliovirus type 3 antigen (formaldehyde inactivated); parent_key: DB10795.", + "name: Dysport; ingredients: Botulinum toxin type A; parent_key: DB00083.", + "name: Nu-diltiaz Tab 60mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: Diltiazem-60 Tab 60mg; ingredients: Diltiazem; parent_key: DB00343.", + "name: For-2; ingredients: Beta carotene + Biotin + Calcium + Calcium ascorbate + Cholecalciferol + Choline + Chromium + Copper + Cyanocobalamin + Folic acid + Inositol + Iodine + Iron + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Selenium + Thiamine + Vitamin A + Vitamin E + Zinc; parent_key: DB00162.", + "name: Calcium Citrate With Vitamin D; ingredients: Calcium + Cholecalciferol; parent_key: DB00169.", + "name: Mega Plex IV - Pck; ingredients: Ascorbic acid + Ascorbic acid + Ascorbic acid + Beta carotene + Beta carotene + Beta carotene + Biotin + Biotin + Calcium + Calcium + Capsicum + Choline + Choline + Chromium + Chromium + Cyanocobalamin + Cyanocobalamin + Folic acid + Inositol + Inositol + Iodine + Iodine + Iron + Iron + Magnesium + Magnesium + Manganese + Manganese + Nicotinamide + Nicotinamide + Pantothenic acid + Pantothenic acid + Potassium + Potassium + Pyridoxine + Pyridoxine + Riboflavin + Riboflavin + Selenium + Thiamine + Thiamine + Vanadium + Vanadium + Vitamin D + Vitamin E + Zinc + Zinc + Zinc; parent_key: DB00126.", + "name: Cartia XT; ingredients: Diltiazem; parent_key: DB00343.", + "name: Dysport Aesthetic; ingredients: Botulinum toxin type A; parent_key: DB00083.", + "name: Diltiazem Hydrochloride Extended Release Extended Release; ingredients: Diltiazem; parent_key: DB00343." + ] + }, + { + "example_idx": 88, + "anchor_id": 16377305013634684689, + "positive_id": 11255592931076654185, + "join_paths": [ + [ + 7, + 42, + 0.30859375 + ], + [ + 4, + 42, + 0.291015625 + ], + [ + 7, + 5, + 0.28125 + ], + [ + 7, + 22, + 0.28125 + ], + [ + 7, + 25, + 0.27734375 + ] + ], + "rows": [ + "The aim of this study was to evaluate a strategy based on a physiologically based pharmacokinetic (PBPK) model for the prediction of PK profiles in human using in vitro data when elimination of compounds relies on active transport processes.", + "The strategy was first applied to rat in vivo and in vitro data in order to refine the PBPK model.", + "The model could then be applied to human in vitro uptake transport data using valsartan as a probe substrate.", + "Plated rat and human hepatocytes, and cell lines overexpressing human OATP1B1 and OATP1B3 were used for in vitro uptake experiments.", + "The uptake rate of valsartan was higher for rat hepatocytes (K (m,u) = 28.4 +/- 3.7 muM, V (max) = 1318 +/- 176 pmol/mg/min and P (dif) = 1.21 +/- 0.42 microl/mg/min) compared to human hepatocytes (K (m,u) = 44.4 +/- 14.6 microM, V (max) = 304 +/- 85 pmol/mg/min and P (dif) = 0.724 +/- 0.271 microl/mg/min).", + "OATP1B1 and 1B3 parameters were correlated to human hepatocyte data using experimentally established relative activity factors (RAF).", + "Resulting PBPK simulations using those in vitro data were compared for plasma (human and rat) and bile (rat) concentration-time profiles following i.v.", + "bolus administration of valsartan.", + "An uncertainty analysis indicated that the scaled in vitro uptake clearance had to be adjusted with an additional empirical scaling factor of 5 to match the plasma concentrations and biliary excretion profiles.", + "Applying this model, plasma clearances (CL(P)) for rat and human were predicted within two-fold relative to predictions based on respective in vitro data.", + "The corrected hepatic uptake transport kinetic parameters enabled the prediction of valsartan in vivo PK profiles and plasma clearances, using PBPK modeling.", + "Moreover, the interspecies difference in elimination rate observed in vivo was correctly reflected in the transport parameters determined in vitro.", + "More data are needed to support more general applications of the proposed approach including its use for metabolized compounds.", + "Administration, Oral\nAdult\nAged\nAngiotensin II Type 1 Receptor Blockers\nAnimals\nBile\nBiological Transport, Active\nCHO Cells\nCricetinae\nCricetulus\nCross-Over Studies\nDrug Interactions\nFemale\nHepatocytes\nHumans\nInjections, Intravenous\nLiver-Specific Organic Anion Transporter 1\nMale\nMiddle Aged\nModels, Biological\nOrganic Anion Transporters\nOrganic Anion Transporters, Sodium-Independent\nRandomized Controlled Trials as Topic\nRats\nRats, Sprague-Dawley\nRats, Wistar\nReproducibility of Results\nSolute Carrier Organic Anion Transporter Family Member 1B3\nSpecies Specificity\nTetrazoles\nTransfection\nValine\nValsartan" + ], + "sentences": [ + "name: Novolin Ge 50/50 Penfill; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Exubera; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Actraphane 30 Innolet; ingredients: Insulin human; parent_key: DB00030.", + "name: Multivitamins and Minerals Tablets; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Beta carotene + Biotin + Calcium + Calcium Phosphate + Cholecalciferol + Chromic chloride + Cupric sulfate + Cyanocobalamin + Ferrous fumarate + Folic acid + Magnesium + Manganese + Nickel sulfate + Nicotinamide + Pantothenic acid + Potassium + Potassium chloride + Potassium Iodide + Pyridoxine + Riboflavin + Selenious acid + Silicon + Sodium metavanadate + Sodium molybdate + Stannous chloride + Thiamine + Vitamin A + Zinc; parent_key: DB00115.", + "name: Aminosyn-PF 10%; ingredients: Alanine + Arginine + Aspartic acid + Glutamic acid + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Methionine + Phenylalanine + Proline + Serine + Taurine + Threonine + Tryptophan + Tyrosine + Valine; parent_key: DB00149.", + "name: Valsartan-hctz; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00999.", + "name: Entresto; ingredients: Sacubitril + Valsartan; parent_key: DB00177.", + "name: Plasma Protein Fraction (human) Protenate; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Afrezza; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Teva-valsartan/hctz; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00177.", + "name: Novolin70/30 70/30; ingredients: Insulin human; parent_key: DB00030.", + "name: Quixil; ingredients: Calcium chloride + Fibrinogen human + Human thrombin; parent_key: DB01164.", + "name: Imprida HCT; ingredients: Amlodipine + Hydrochlorothiazide + Valsartan; parent_key: DB00381.", + "name: Humulin U; ingredients: Insulin human; parent_key: DB00030.", + "name: Diovan 80mg; ingredients: Valsartan; parent_key: DB00177.", + "name: EVICEL Fibrin Sealant (Human); ingredients: Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: Insuman Comb 50; ingredients: Insulin human; parent_key: DB00030.", + "name: PMS-valsartan-hctz; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00177.", + "name: TrophAmine; ingredients: Alanine + Arginine + Aspartic acid + Cysteine + Glutamic acid + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Methionine + N-acetyltyrosine + Phenylalanine + Proline + Serine + Taurine + Threonine + Tryptophan + Tyrosine + Valine; parent_key: DB00150.", + "name: Hemasate Ultra Hs3150; ingredients: Calcium chloride + Citric acid + Dextrose, unspecified form + Magnesium chloride + Potassium chloride + Sodium chloride; parent_key: DB01164.", + "name: TrophAmine; ingredients: Alanine + Arginine + Aspartic acid + Cysteine + Glutamic acid + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Methionine + N-acetyltyrosine + Phenylalanine + Proline + Serine + Taurine + Threonine + Tryptophan + Tyrosine + Valine; parent_key: DB00151.", + "name: Q-valsartan Hctz; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00999.", + "name: Amlodipine and Valsartan; ingredients: Amlodipine + Valsartan; parent_key: DB00177.", + "name: Ava-valsartan HCT; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00177.", + "name: NovolinN N; ingredients: Insulin human; parent_key: DB00030.", + "name: Valsartan-hctz; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00177.", + "name: Jamp-electropeg With Flavour Packet; ingredients: Polyethylene glycol + Potassium chloride + Sodium bicarbonate + Sodium chloride + Sodium sulfate; parent_key: DB00761.", + "name: AMLODIPINE and VALSARTAN; ingredients: Amlodipine + Valsartan; parent_key: DB00381.", + "name: Acid Concentrate Ro4132; ingredients: Acetic acid + Calcium chloride + Dextrose, unspecified form + Magnesium chloride + Sodium chloride; parent_key: DB01164.", + "name: EVICEL Fibrin Sealant (Human); ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222.", + "name: Amlodipine-valsartan Mylan; ingredients: Amlodipine + Valsartan; parent_key: DB00177.", + "name: Amlodipine, Valsartan, Hydrochlorothiazide; ingredients: Amlodipine + Hydrochlorothiazide + Valsartan; parent_key: DB00381.", + "name: Afrezza; ingredients: Insulin human + Insulin human + Insulin human; parent_key: DB00030.", + "name: Naturalyte H-615; ingredients: Acetic acid + Calcium chloride + Dextrose, unspecified form + Magnesium chloride + Potassium chloride + Sodium chloride; parent_key: DB00761.", + "name: Humulin N (kwikpen); ingredients: Insulin human; parent_key: DB00030.", + "name: Raplixa; ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222.", + "name: Exforge HCT; ingredients: Amlodipine + Hydrochlorothiazide + Valsartan; parent_key: DB00999.", + "name: Aminosyn II 7% With 10% Dextrose; ingredients: Alanine + Arginine + Aspartic acid + Dextrose, unspecified form + Glutamic acid + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Methionine + N-acetyltyrosine + Phenylalanine + Proline + Serine + Threonine + Tryptophan + Valine; parent_key: DB00133.", + "name: Insulin Human Winthrop Comb 15; ingredients: Insulin human; parent_key: DB00030.", + "name: Pneumovax 23; ingredients: Streptococcus pneumoniae type 1 capsular polysaccharide antigen + Streptococcus pneumoniae type 10a capsular polysaccharide antigen + Streptococcus pneumoniae type 11a capsular polysaccharide antigen + Streptococcus pneumoniae type 12f capsular polysaccharide antigen + Streptococcus pneumoniae type 14 capsular polysaccharide antigen + Streptococcus pneumoniae type 15b capsular polysaccharide antigen + Streptococcus pneumoniae type 17f capsular polysaccharide antigen + Streptococcus pneumoniae type 18c capsular polysaccharide antigen + Streptococcus pneumoniae type 19a capsular polysaccharide antigen + Streptococcus pneumoniae type 19f capsular polysaccharide antigen + Streptococcus pneumoniae type 2 capsular polysaccharide antigen + Streptococcus pneumoniae type 20 capsular polysaccharide antigen + Streptococcus pneumoniae type 22f capsular polysaccharide antigen + Streptococcus pneumoniae type 23f capsular polysaccharide antigen + Streptococcus pneumoniae type 3 capsular polysaccharide antigen + Streptococcus pneumoniae type 33f capsular polysaccharide antigen + Streptococcus pneumoniae type 4 capsular polysaccharide antigen + Streptococcus pneumoniae type 5 capsular polysaccharide antigen + Streptococcus pneumoniae type 6b capsular polysaccharide antigen + Streptococcus pneumoniae type 7f capsular polysaccharide antigen + Streptococcus pneumoniae type 8 capsular polysaccharide antigen + Streptococcus pneumoniae type 9n capsular polysaccharide antigen + Streptococcus pneumoniae type 9v capsular polysaccharide antigen; parent_key: DB10329.", + "name: Mylan-valsartan Hctz; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00177.", + "name: Vistaseal; ingredients: Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: Valsartan HCT; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00999.", + "name: Prexxartan; ingredients: Valsartan; parent_key: DB00177.", + "name: Diovan HCT; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00177.", + "name: Auro-valsartan HCT; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00177.", + "name: Teva-valsartan; ingredients: Valsartan; parent_key: DB00177.", + "name: Novo-valsartan/hctz; ingredients: Hydrochlorothiazide + Valsartan; parent_key: DB00177.", + "name: Novolin Ge Toronto; ingredients: Insulin human; parent_key: DB00030.", + "name: Amlodipine and Valsartan; ingredients: Amlodipine + Valsartan; parent_key: DB00381." + ] + }, + { + "example_idx": 89, + "anchor_id": 17077135964961539786, + "positive_id": 14946671093229809076, + "join_paths": [ + [ + 8, + 28, + 0.373046875 + ], + [ + 3, + 28, + 0.3671875 + ], + [ + 3, + 37, + 0.359375 + ], + [ + 8, + 4, + 0.35546875 + ], + [ + 8, + 37, + 0.35546875 + ] + ], + "rows": [ + "PURPOSE: Latanoprost, a prostaglandin F(2alpha) analogue, has become one of the most widely used medications for the treatment of glaucoma.", + "The authors hypothesized that organic anion transporting polypeptides (OATPs) are responsible for the uptake of latanoprost into ocular tissues and, hence, that they contribute to the interindividual differences in drug concentrations and effects.", + "METHODS: Expression of prostaglandin (PG) transporters (OATP2A1, OATP2B1) in human ocular tissues was determined using real-time RT-PCR and immunofluorescence.", + "The inhibitory interactions between latanoprost and its active metabolite (the free acid) and the uptake of prototypical substrates (PGE(2) and bromosulfophthalein) were tested in stably transfected human embryonic kidney cells overexpressing either OATP2A1 or OATP2B1.", + "These cells were also used to investigate whether latanoprost and latanoprost acid are substrates of OATP2A1 or OATP2B1.", + "RESULTS: OATP2A1 and OATP2B1 mRNA expression was highest in the choroid/retinal pigment epithelium (RPE) complex and ciliary body.", + "OATP2A1 protein expression was most prominent in the RPE and in epithelial and endothelial cell layers of anterior segment tissues, such as cornea, conjunctiva, iris, and ciliary body, whereas OATP2B1 protein was additionally expressed in trabecular meshwork, Schlemm canal, and choroidal vasculature.", + "Latanoprost and latanoprost acid significantly inhibited both OATP2A1 and OATP2B1.", + "Uptake experiments demonstrated that latanoprost acid is effectively transported by OATP2A1 (affinity constant [K(m)], 5.4 microM; maximum uptake rate [V(max)], 21.5 pmol/mg protein/min) and less effectively by OATP2B1.", + "CONCLUSIONS: The results presented herein suggest that at least OATP2A1 plays a role in the intraocular disposition of the therapeutically used prostanoid latanoprost.", + "Aged\nAged, 80 and over\nAnterior Eye Segment\nAntihypertensive Agents\nBiological Transport\nCell Line\nChoroid\nChromatography, Liquid\nFemale\nFluorescent Antibody Technique, Indirect\nGene Expression Regulation\nGlaucoma\nHumans\nIntraocular Pressure\nKidney\nLatanoprost\nMale\nMiddle Aged\nOrganic Anion Transporters\nProstaglandins F, Synthetic\nRNA, Messenger\nRetinal Pigment Epithelium\nReverse Transcriptase Polymerase Chain Reaction\nTandem Mass Spectrometry\nTransfection" + ], + "sentences": [ + "name: Riva-latanoprost/timolol; ingredients: Latanoprost + Timolol; parent_key: DB00654.", + "name: Prenate Mini; ingredients: Ascorbic acid + Biotin + Calcium carbonate + Cholecalciferol + Cyanocobalamin + DL-alpha tocopheryl acetate + Doconexent + Ferrous asparto glycinate + Folic acid + Iron + Levomefolic acid + Lowbush blueberry + Magnesium oxide + Potassium Iodide + Pyridoxine; parent_key: DB00115.", + "name: SOMA Atocell; ingredients: Trametes versicolor fruiting body; parent_key: DB14287.", + "name: SOMA Diat; ingredients: Trametes versicolor fruiting body; parent_key: DB14287.", + "name: Bl Latanoprost; ingredients: Latanoprost; parent_key: DB00654.", + "name: Xalacom; ingredients: Latanoprost + Timolol; parent_key: DB00373.", + "name: Yellow Jacket hymenoptera venom Venomil Diagnostic; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Membraneblue; ingredients: Trypan blue free acid; parent_key: DB09158.", + "name: Sandoz Latanoprost/timolol; ingredients: Latanoprost + Timolol; parent_key: DB00654.", + "name: Hymenoptera Venom Product-mixed Vespid Venom Protein (1650 Mcg); ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB10958.", + "name: Apo-latanoprost-timop; ingredients: Latanoprost + Timolol; parent_key: DB00654.", + "name: Tropicana Calcium & Vitamin C Supplement; ingredients: Ascorbic acid + Calcium; parent_key: DB00126.", + "name: Mixed Vespid Hymenoptera Venom Multidose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11032.", + "name: Tim-Brim-Dor-Lat; ingredients: Brimonidine + Dorzolamide + Latanoprost + Timolol; parent_key: DB00869.", + "name: Mixed Vespid hymenoptera venom Venomil Maintenance; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB10957.", + "name: Pharmalgen Mixed Vespid Venom Protein; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Mixed Vespid Venom Protein Multidose 13.0 Ml (3900 Mcg); ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Bebulin Vh Inj 1000unit/vial; ingredients: Factor IX Complex (Human) + Water; parent_key: DB11330.", + "name: Venomil Inj Mixed 300mcg/dose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB10957.", + "name: Imm Formula; ingredients: Ascorbic acid + Zinc; parent_key: DB00126.", + "name: Tim-Brim-Dor-Lat; ingredients: Brimonidine + Dorzolamide + Latanoprost + Timolol; parent_key: DB00654.", + "name: Yellow Jacket hymenoptera venom Venomil Diagnostic; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11032.", + "name: Mixed Vespid Hymenoptera Venom Multidose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB10958.", + "name: Tim-Dor-Lat; ingredients: Dorzolamide + Latanoprost + Timolol; parent_key: DB00869.", + "name: Nutra-clear; ingredients: Ascorbic acid + Biotin + Calcium + Chromium + Copper + Cyanocobalamin + Dipotassium phosphate + Folic acid + Magnesium + Manganese + Molybdenum + Nicotinamide + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Thiamine + Vitamin A + Vitamin E + Zinc; parent_key: DB00115.", + "name: SOMA Heart-Q; ingredients: Trametes versicolor fruiting body; parent_key: DB14287.", + "name: Rocklatan; ingredients: Latanoprost + Netarsudil; parent_key: DB13931.", + "name: Ortho-Nesic; ingredients: Levomenthol + Synthetic camphor; parent_key: DB14156.", + "name: Jamp Latanoprost; ingredients: Latanoprost; parent_key: DB00654.", + "name: Venomil Mixed Vespid Venom Protein (360mcg); ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Mixed Vespid Venom Protein Inj; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Mixed Vespid hymenoptera venom Venomil Maintenance; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB10956.", + "name: Yellow Jacket hymenoptera venom Venomil Maintenance; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11032.", + "name: Gd-latanoprost/timolol; ingredients: Latanoprost + Timolol; parent_key: DB00654.", + "name: Humulin 40/60 Cartridge; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Aminosyn-PF 10%; ingredients: Alanine + Arginine + Aspartic acid + Glutamic acid + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Methionine + Phenylalanine + Proline + Serine + Taurine + Threonine + Tryptophan + Tyrosine + Valine; parent_key: DB00133.", + "name: Med-latanoprost-timolol; ingredients: Latanoprost + Timolol; parent_key: DB00654.", + "name: Latanoprost PF; ingredients: Latanoprost; parent_key: DB00654.", + "name: Hymenoptera Venom Diagnostic; ingredients: Apis mellifera venom + Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Polistes fuscatus venom protein + Vespula maculifrons venom protein; parent_key: DB10955.", + "name: Xalatan; ingredients: Latanoprost; parent_key: DB00654.", + "name: Yellow Jacket hymenoptera venom Multidose; ingredients: Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Navy Bean; ingredients: Kidney bean; parent_key: DB10639.", + "name: Hymenoptera Venom Product-mixed Vespid Venom Protein (1650 Mcg); ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB10957.", + "name: Red Kidney Beans; ingredients: Kidney bean; parent_key: DB10639.", + "name: Floriva Plus; ingredients: alpha-Tocopherol succinate + Ascorbic acid + Cholecalciferol + Cyanocobalamin + Flavin mononucleotide + Levomefolic acid + Nicotinamide + Pyridoxine + Sodium fluoride + Thiamine + Vitamin A; parent_key: DB00115.", + "name: Mixed Vespid Hymenoptera Venom Multidose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB10956.", + "name: Vaxelis; ingredients: Bordetella pertussis filamentous hemagglutinin antigen (formaldehyde inactivated) + Bordetella pertussis fimbriae 2/3 antigen + Bordetella pertussis pertactin antigen + Bordetella pertussis toxoid antigen (glutaraldehyde inactivated) + Clostridium tetani toxoid antigen (formaldehyde inactivated) + Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) + Haemophilus influenzae type B capsular polysaccharide meningococcal outer membrane protein conjugate antigen + Hepatitis B Vaccine (Recombinant) + Poliovirus type 1 antigen (formaldehyde inactivated) + Poliovirus type 2 antigen (formaldehyde inactivated) + Poliovirus type 3 antigen (formaldehyde inactivated); parent_key: DB10795.", + "name: Hymenoptera Venom Product-mixed Vespid Venom Protein (1650 Mcg); ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Jamp-latanoprost/timolol; ingredients: Latanoprost + Timolol; parent_key: DB00654.", + "name: Vistaseal; ingredients: Fibrinogen human + Human thrombin; parent_key: DB11571." + ] + }, + { + "example_idx": 90, + "anchor_id": 8472596991162164499, + "positive_id": 16068574293952052118, + "join_paths": [ + [ + 0, + 4, + 0.2001953125 + ], + [ + 0, + 13, + 0.17578125 + ], + [ + 0, + 17, + 0.17578125 + ], + [ + 10, + 4, + 0.1669921875 + ], + [ + 2, + 19, + 0.1611328125 + ] + ], + "rows": [ + "IMPORTANCE OF THE FIELD: Inhibition of platelet aggregation plays a key role in treatment of coronary artery disease.", + "AREAS COVERED IN THIS REVIEW: Studies on the effects of tirofiban in patients with either ST elevation or non-ST elevation myocardial infarction are reviewed.", + "WHAT THE READER WILL GAIN: Tirofiban is a small-molecule glycoprotein IIb/IIIa receptor inhibitor.", + "If discontinued, the action of tirofiban is faster reversed as abciximab.", + "The dose varied between low (bolus of 0.4 microg/kg administered over 30 min followed by an infusion of 0.10 microg/kg/min), intermediate (bolus of 10 microg/kg administered over 3 min followed by an infusion of 0.15 microg/kg/min) and high (bolus of 25 microg/kg administered over 3 min followed by an infusion of 0.15 microg/kg/min).", + "The high-dose administration especially may be beneficial in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI).", + "There is no indication for tirofiban in patients treated with thrombolysis.", + "Patients with non-ST elevation myocardial infarction requiring PCI are most likely to benefit from tirofiban if they have ongoing ischemia and/or dynamic ECG changes.", + "The risk of serious bleeding with tirofiban is low and there is a very low risk of thrombocytopenia.", + "TAKE HOME MESSAGE: Use of tirofiban for myocardial infarction is effective and has an acceptable safety profile.", + "Angioplasty, Balloon, Coronary\nDose-Response Relationship, Drug\nElectrocardiography\nHemorrhage\nHumans\nMyocardial Infarction\nPlatelet Aggregation Inhibitors\nPlatelet Glycoprotein GPIIb-IIIa Complex\nThrombocytopenia\nTirofiban\nTyrosine" + ], + "sentences": [ + "id: BE0002098; name: Low affinity immunoglobulin gamma Fc region receptor II-a; organism: Humans; known_action: unknown; position: 5; parent_key: DB00087.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB13953.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: yes; position: 1; parent_key: DB14065.", + "id: BE0002854; name: Beta-2-glycoprotein 1; organism: Humans; known_action: unknown; position: 123; parent_key: DB09130.", + "id: BE0000866; name: Platelet glycoprotein IX; organism: Humans; known_action: unknown; position: 2; parent_key: DB00468.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB06871.", + "id: BE0002100; name: Low affinity immunoglobulin gamma Fc region receptor II-c; organism: Humans; known_action: unknown; position: 5; parent_key: DB00005.", + "id: BE0009047; name: Alpha-1B-glycoprotein; organism: Humans; known_action: unknown; position: 110; parent_key: DB09130.", + "id: BE0003438; name: Alpha-7 nicotinic cholinergic receptor subunit; organism: Humans; known_action: unknown; position: 1; parent_key: DB01520.", + "id: BE0002097; name: Low affinity immunoglobulin gamma Fc region receptor III-A; organism: Humans; known_action: unknown; position: 6; parent_key: DB11767.", + "id: BE0000901; name: Low affinity immunoglobulin gamma Fc region receptor III-B; organism: Humans; known_action: unknown; position: 2; parent_key: DB00002.", + "id: BE0000499; name: Low-density lipoprotein receptor; organism: Humans; known_action: unknown; parent_key: DB00707.", + "id: BE0000852; name: Platelet-derived growth factor receptor alpha; organism: Humans; known_action: yes; parent_key: DB06043.", + "id: BE0005561; name: Platelet-activating factor receptor; organism: Humans; known_action: yes; position: 5; parent_key: DB11614.", + "id: BE0003411; name: Platelet-derived growth factor D; organism: Humans; known_action: unknown; parent_key: DB05465.", + "id: BE0000901; name: Low affinity immunoglobulin gamma Fc region receptor III-B; organism: Humans; known_action: unknown; position: 2; parent_key: DB00087.", + "id: BE0000687; name: Thyroid hormone receptor alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB00509.", + "id: BE0005561; name: Platelet-activating factor receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB09166.", + "id: BE0000439; name: Integrin alpha-IIb; organism: Humans; known_action: yes; position: 2; parent_key: DB00054.", + "id: BE0000901; name: Low affinity immunoglobulin gamma Fc region receptor III-B; organism: Humans; known_action: unknown; position: 3; parent_key: DB00111.", + "id: BE0002099; name: Low affinity immunoglobulin gamma Fc region receptor II-b; organism: Humans; known_action: unknown; position: 4; parent_key: DB00054.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; parent_key: DB06240.", + "id: BE0002708; name: U1 small nuclear ribonucleoprotein A; organism: Humans; known_action: unknown; parent_key: DB02175.", + "id: BE0002098; name: Low affinity immunoglobulin gamma Fc region receptor II-a; organism: Humans; known_action: unknown; position: 4; parent_key: DB11767.", + "id: BE0000852; name: Platelet-derived growth factor receptor alpha; organism: Humans; known_action: unknown; position: 6; parent_key: DB00619.", + "id: BE0002345; name: Gamma-aminobutyric acid receptor subunit beta-3; organism: Humans; known_action: yes; position: 10; parent_key: DB01567.", + "id: BE0002097; name: Low affinity immunoglobulin gamma Fc region receptor III-A; organism: Humans; known_action: unknown; position: 6; parent_key: DB00002.", + "id: BE0009495; name: Myosin-IIIa; organism: Humans; known_action: unknown; position: 218; parent_key: DB12010.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; parent_key: DB00373.", + "id: BE0009324; name: Bone morphogenetic protein receptor type-2; organism: Humans; known_action: unknown; position: 72; parent_key: DB12010.", + "id: BE0000439; name: Integrin alpha-IIb; organism: Humans; known_action: unknown; parent_key: DB04863.", + "id: BE0002098; name: Low affinity immunoglobulin gamma Fc region receptor II-a; organism: Humans; known_action: unknown; position: 3; parent_key: DB00054.", + "id: BE0002099; name: Low affinity immunoglobulin gamma Fc region receptor II-b; organism: Humans; known_action: yes; position: 4; parent_key: DB00028.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; parent_key: DB01107.", + "id: BE0002098; name: Low affinity immunoglobulin gamma Fc region receptor II-a; organism: Humans; known_action: unknown; position: 8; parent_key: DB00002.", + "id: BE0000852; name: Platelet-derived growth factor receptor alpha; organism: Humans; known_action: yes; position: 8; parent_key: DB01268.", + "id: BE0003663; name: Alpha-1-acid glycoprotein 2; organism: Humans; known_action: unknown; position: 12; parent_key: DB00281.", + "id: BE0001085; name: Intercellular adhesion molecule 1; organism: Humans; known_action: unknown; position: 6; parent_key: DB12598.", + "id: BE0003411; name: Platelet-derived growth factor D; organism: Humans; known_action: unknown; parent_key: DB05139.", + "id: BE0000437; name: Cyclin-dependent kinase 15; organism: Humans; known_action: unknown; position: 243; parent_key: DB12010.", + "id: BE0000901; name: Low affinity immunoglobulin gamma Fc region receptor III-B; organism: Humans; known_action: unknown; position: 7; parent_key: DB00005.", + "id: BE0000562; name: Low affinity cationic amino acid transporter 2; organism: Humans; known_action: unknown; parent_key: DB00123.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: yes; position: 1; parent_key: DB14061.", + "id: BE0000659; name: 5-hydroxytryptamine receptor 1D; organism: Humans; known_action: unknown; position: 8; parent_key: DB00363.", + "id: BE0000942; name: Low-density lipoprotein receptor-related protein 2; organism: Humans; known_action: no; position: 3; parent_key: DB00798.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: yes; position: 1; parent_key: DB14069.", + "id: BE0000901; name: Low affinity immunoglobulin gamma Fc region receptor III-B; organism: Humans; known_action: unknown; position: 7; parent_key: DB11767.", + "id: BE0000439; name: Integrin alpha-IIb; organism: Humans; known_action: yes; position: 1; parent_key: DB00775.", + "id: BE0000942; name: Low-density lipoprotein receptor-related protein 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB00013.", + "id: BE0000901; name: Low affinity immunoglobulin gamma Fc region receptor III-B; organism: Humans; known_action: unknown; position: 5; parent_key: DB00075." + ] + }, + { + "example_idx": 92, + "anchor_id": 11549515730330657598, + "positive_id": 16075427615350556521, + "join_paths": [ + [ + 0, + 25, + 0.298828125 + ], + [ + 2, + 28, + 0.294921875 + ], + [ + 2, + 32, + 0.29296875 + ], + [ + 2, + 36, + 0.291015625 + ], + [ + 0, + 28, + 0.28515625 + ] + ], + "rows": [ + "BACKGROUND: The potential of gemcitabine to interact with carboplatin was explored in a phase II trial in platinum-resistant ovarian cancer.", + "Peripheral blood lymphocytes were sampled after drug administration to measure DNA interstrand cross-link formation and repair.", + "PATIENTS AND METHODS: Forty patients received carboplatin target area under concentration-time curve (AUC 4) followed by gemcitabine 1,000 mg/m(2) with a second dose of gemcitabine on day 8.", + "Peripheral blood lymphocytes were obtained in 12 patients before and at intervals during the first cycle of chemotherapy.", + "DNA cross-link formation and repair (unhooking) were measured by the single-cell gel electrophoresis (comet) assay following ex vivo incubation.", + "RESULTS: The global response rate was 47% (Response Evaluation Criteria in Solid Tumors rate, 29%; CA125 rate, 63%).", + "Delays in treatment were seen in 24% of cycles largely due to myelosuppression; 15% of day 8 administration was omitted.", + "Peak carboplatin-induced DNA cross-linking was seen by 24 hours.", + "Significant reduction was seen in the repair of in vivo carboplatin-induced DNA cross-links following administration of gemcitabine.", + "CONCLUSION: An enhanced activity of carboplatin in platinum-resistant ovarian cancer may be due to synergy with gemcitabine through inhibition of repair of DNA cross-links.", + "Future studies should explore coadministration of these drugs, as this may be a more effective schedule.", + "Aged\nAged, 80 and over\nAntineoplastic Agents\nCarboplatin\nDNA Damage\nDNA Repair\nDNA, Neoplasm\nDeoxycytidine\nDose-Response Relationship, Drug\nDrug Resistance, Neoplasm\nFemale\nHumans\nMiddle Aged\nOvarian Neoplasms\nPlatinum Compounds\nTime Factors\nTreatment Outcome" + ], + "sentences": [ + "name: Keloid Healer Synergy for treatment of keloids; ingredients: Balsam of Peru + Eucalyptol; parent_key: DB11482.", + "name: Aj-gemcitabine; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Luvira; ingredients: (12R)-12-hydroxyeicosapentaenoic acid + Doconexent + Omega-3 fatty acids; parent_key: DB03756.", + "name: HUCORD HSCM-100 Ampoule; ingredients: Insulin-like growth factor II; parent_key: DB14472.", + "name: Quick Defense 4m Disinfectant Wipes; ingredients: Benzalkonium + Didecyldimethylammonium + Dioctyldimonium + Quaternium-24; parent_key: DB13969.", + "name: Carboplatin Injection; ingredients: Carboplatin; parent_key: DB00958.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB00994.", + "name: Gemcitabine hydrochloride; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Antiscar; ingredients: 13-cis-12-(3'-Carboxyphenyl)retinoic acid + Allantoin + Epigallocatechin gallate + Onion + Petrolatum; parent_key: DB12116.", + "name: O Hui Wrinkle Science Wrinkle Repair Serum; ingredients: Methoxy PEG-12 retinamide; parent_key: DB14142.", + "name: ISA KNOX X2D2 WRINKLE Serum; ingredients: Methoxy PEG-12 retinamide; parent_key: DB14142.", + "name: Giapreza; ingredients: Angiotensin II; parent_key: DB11842.", + "name: Isa Knox Wrinkle Decline Double Effect Rf3 Serum; ingredients: Methoxy PEG-12 retinamide; parent_key: DB14142.", + "name: Paraplatin; ingredients: Carboplatin; parent_key: DB00958.", + "name: Quick Defense 4m Disinfectant Wipes; ingredients: Benzalkonium + Didecyldimethylammonium + Dioctyldimonium + Quaternium-24; parent_key: DB13970.", + "name: Freeman Packing Hand Sanitizer 005; ingredients: C11-12 isoparaffin; parent_key: DB11329.", + "name: CARBOplatin; ingredients: Carboplatin; parent_key: DB00958.", + "name: Paraplatin Inj 150mg/vial; ingredients: Carboplatin; parent_key: DB00958.", + "name: Gemzar (1gm/vial); ingredients: Gemcitabine; parent_key: DB00441.", + "name: Afluria; ingredients: Influenza A virus A/Singapore/GP1908/2015 IVR-180A (H1N1) antigen (propiolactone inactivated) + Influenza A virus A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) antigen (propiolactone inactivated) + Influenza B virus B/Maryland/15/2016 antigen (propiolactone inactivated); parent_key: DB14468.", + "name: HemaCord; ingredients: Human cord blood hematopoietic progenitor cell; parent_key: DB11054.", + "name: Carboplatin Injection Liq 10mg/ml; ingredients: Carboplatin; parent_key: DB00958.", + "name: UltraTag RBC; ingredients: Technetium Tc-99m red blood cells; parent_key: DB09493.", + "name: Infugem; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Flucelvax Quadrivalent (prefilled Syringe); ingredients: Influenza A virus A/Singapore/GP1908/2015 IVR-180 (H1N1) antigen (MDCK cell derived, propiolactone inactivated) + Influenza A virus A/Singapore/GP2050/2015 (H3N2) antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Hong Kong/259/2010 antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Utah/9/2014 antigen (MDCK cell derived, propiolactone inactivated); parent_key: DB11002.", + "name: Gemcitabine; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Quick Defense 4m Disinfectant Wipes; ingredients: Benzalkonium + Didecyldimethylammonium + Dioctyldimonium + Quaternium-24; parent_key: DB04221.", + "name: Carboplatin; ingredients: Carboplatin; parent_key: DB00958.", + "name: Gemcitabine for Injection; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Carboplatin Injection, BP; ingredients: Carboplatin; parent_key: DB00958.", + "name: Flublok Quadrivalent; ingredients: Influenza A virus A/Brisbane/02/2018 (H1N1) recombinant hemagglutinin antigen + Influenza A virus A/Kansas/14/2017 (H3N2) recombinant hemagglutinin antigen + Influenza B virus B/Maryland/15/2016 recombinant hemagglutinin antigen + Influenza B virus B/Phuket/3073/2013 recombinant hemagglutinin antigen; parent_key: DB15518.", + "name: Gemcitabine Hydrochloride for Injection; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Gemcitabine Injection; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Carboplatin Injection BP; ingredients: Carboplatin; parent_key: DB00958.", + "name: Paraplatin-AQ Inj 10mg/ml; ingredients: Carboplatin; parent_key: DB00958.", + "name: Flulaval Quadrivalent 2018/2019; ingredients: Influenza A virus A/Singapore/GP1908/2015 IVR-180 (H1N1) antigen (UV, formaldehyde inactivated) + Influenza A virus A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) antigen (UV, formaldehyde inactivated) + Influenza B virus B/Maryland/15/2016 BX-69A antigen (UV, formaldehyde inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (UV, formaldehyde inactivated); parent_key: DB14560.", + "name: Gemcitabine for Injection Concentrate; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Fluarix Quadrivalent 2018/2019; ingredients: Influenza A virus A/Singapore/gp1908/2015 IVR-180 (H1N1) antigen (formaldehyde inactivated) + Influenza A virus A/Singapore/INFIMH-16-0019/2016 NIB-104 (H3N2) antigen (formaldehyde inactivated) + Influenza B virus B/Maryland/15/2016 BX-69A antigen (formaldehyde inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (formaldehyde inactivated); parent_key: DB14461.", + "name: Gemzar; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Gemcitabine HCl; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Gemcitabine Sun for Injection; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Flucelvax; ingredients: Influenza A virus A/Brisbane/10/2010 (H1N1) antigen (MDCK cell derived, propiolactone inactivated) + Influenza A virus A/Victoria/361/2011 IVR-165 (H3N2) antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Wisconsin/1/2010) antigen (MDCK cell derived, propiolactone inactivated); parent_key: DB14608.", + "name: Gemzar (200mg/vial); ingredients: Gemcitabine; parent_key: DB00441.", + "name: Act Gemcitabine; ingredients: Gemcitabine; parent_key: DB00441.", + "name: REFRESH OPTIVE Advanced; ingredients: Carboxymethylcellulose + Glycerin + Polysorbate 80; parent_key: DB09462.", + "name: Quick Defense 4m Disinfectant Wipes; ingredients: Benzalkonium + Didecyldimethylammonium + Dioctyldimonium + Quaternium-24; parent_key: DB11105.", + "name: Gemcitabine Hydrochloride; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Isa Knox X2d2 Wrinkle Corrector; ingredients: Methoxy PEG-12 retinamide; parent_key: DB14142.", + "name: Gemcitabine for Injection USP; ingredients: Gemcitabine; parent_key: DB00441.", + "name: Gemcitabine for Injection, USP; ingredients: Gemcitabine; parent_key: DB00441." + ] + }, + { + "example_idx": 94, + "anchor_id": 8866041466251372557, + "positive_id": 11739858448672389167, + "join_paths": [ + [ + 0, + 9, + 0.28515625 + ], + [ + 4, + 35, + 0.275390625 + ], + [ + 2, + 35, + 0.26953125 + ], + [ + 3, + 35, + 0.259765625 + ], + [ + 1, + 35, + 0.22265625 + ] + ], + "rows": [ + "There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry.", + "N-acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders.", + "Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry.", + "Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways.", + "This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder.", + "N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited.", + "The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research.", + "Acetylcysteine\nHumans\nMental Disorders" + ], + "sentences": [ + "ref-id: L2141; title: Boric Acid - National Toxicology Program - NIH; url: https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr324.pdf; parent_key: DB11326.", + "ref-id: L12147; title: Bempedoic acid: A novel agent (Esperion); url: https://www.esperion.com/science/bempedoic-acid/; parent_key: DB11936.", + "ref-id: L14294; title: Product monograph: Rasilez HCT (Aliskiren fumarate and hydrochlorothiazide oral tablets); url: https://www.novartis.ca/sites/www.novartis.ca/files/rasilez%20hct_scrip_e.pdf; parent_key: DB09026.", + "ref-id: L547; title: Skin care research; url: http://www.smartskincare.com/skinprotection/sunblocks/sunblock_octocylene.html; parent_key: DB09535.", + "ref-id: L1867; title: National Institute for Health Research; url: http://www.io.nihr.ac.uk/wp-content/uploads/migrated/Vonicog-alfa-Feb16.pdf; parent_key: DB12872.", + "ref-id: L1427; title: Anxiety- rather than depression-like behavior is associated with adult neurogenesis in a female mouse model of higher trait anxiety- and comorbid depression-like behavior; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565824/; parent_key: DB09289.", + "ref-id: L1636; title: Therapeutic potential for novel drugs targeting the type 1 cholecystokinin receptor; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839260/; parent_key: DB08862.", + "ref-id: L752; title: Magnesium Absorption in Humans ; url: http://e-collection.library.ethz.ch/eserv/eth:26387/eth-26387-02.pdf; parent_key: DB09409.", + "ref-id: L1816; title: European Medicines Agency: Benzalkonium chloride used as an excipient; url: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2017/10/WC500235907.pdf; parent_key: DB11105.", + "ref-id: L5995; title: Dehli Psychiatry Journal paper; url: http://medind.nic.in/daa/t12/i2/daat12i2p402.pdf; parent_key: DB01142.", + "ref-id: L1375; title: National Institute of Mental Health; url: https://www.nimh.nih.gov/health/topics/depression/index.shtml; parent_key: DB01247.", + "ref-id: L2478; title: Absorption, Biotransformation, and Pharmacokinetics of Salicylsalicylic Acid in Humans; url: https://www.researchgate.net/publication/15889003_Absorption_Biotransformation_and_Pharmacokinetics_of_Salicylsalicylic_Acid_in_Humans; parent_key: DB11071.", + "ref-id: L315; title: CENTER FOR DRUG EVALUATION AND RESEARCH ; url: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209115Orig1s000MultiDisciplineR.pdf; parent_key: DB12332.", + "ref-id: L1609; title: CHOLECYSTOGRAPHIC AGENT: A RE-EVALUATION OF ITS CLINICAL UTILITY; url: https://vdocuments.site/prolonged-treatment-of-hyperthyroidism-with-sodium-tyropanoate-an-oral-cholecystographic.html; parent_key: DB09340.", + "ref-id: L1867; title: National Institute for Health Research; url: http://www.io.nihr.ac.uk/wp-content/uploads/migrated/Vonicog-alfa-Feb16.pdf; parent_key: DB13133.", + "ref-id: L1024; title: European Medicines Agency (EMA) Summary of product characteristics: Selincro; url: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002583/WC500140255.pdf; parent_key: DB06230.", + "ref-id: L2213; title: The emerging role of zinc transporters; url: https://www.nature.com/articles/sigtrans201729; parent_key: DB01593.", + "ref-id: L2523; title: Psychiatric uses of Meratran; url: https://www.cambridge.org/core/journals/journal-of-mental-science/article/psychiatric-uses-of-meratran/3E82BB0C7B9BAF79D98065ECD971ECCB; parent_key: DB11584.", + "ref-id: L1667; title: Pharmacological science; url: https://www.pharmacologicalsciences.us/pharmaceutical-chemistry/monoclonal-antibody-radionuclide-test-kits.html; parent_key: DB09336.", + "ref-id: L1522; title: Current antipsychotics; url: https://books.google.ca/books?id=RpVtM_WVw64C&pg=PA258&lpg=PA258&dq=PIPAMPERONE+metabolism&source=bl&ots=jl4_fNIg92&sig=bBV2ZA-BLObu-ukpCv7fXsTOfvg&hl=en&sa=X&ved=0ahUKEwjFrtHr6NXZAhXFz1QKHeNPBnoQ6AEIczAJ#v=onepage&q=PIPAMPERONE%20metabolism&f=false; parent_key: DB09286.", + "ref-id: L1498; title: The pharmacokinetics and availability of niflumic acid in humans; url: https://www.researchgate.net/publication/16346020_The_pharmacokinetics_and_availability_of_niflumic_acid_in_humans; parent_key: DB09285.", + "ref-id: L2107; title: Zinc homeostasis in humans; url: https://academic.oup.com/jn/article/130/5/1360S/4686372; parent_key: DB14487.", + "ref-id: L1979; title: NIH.gov Topical Therapies in psoriasis; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518573/; parent_key: DB11157.", + "ref-id: L1621; title: Rauwolfia Serpentina in the Treatment of High Blood Pressure A Review of the Literature; url: http://circ.ahajournals.org/content/12/2/220; parent_key: DB09363.", + "ref-id: L2091; title: Zinc Toxicity in Humans; url: https://pdfs.semanticscholar.org/a9e2/8321ae506e646f32ce59d87b7589851aa7e4.pdf; parent_key: DB01593.", + "ref-id: L1374; title: Relationship between pharmacokinetics and pharmacodynamics of molsidomine and its metabolites in humans; url: http://europepmc.org/abstract/med/3838400; parent_key: DB09282.", + "ref-id: L145; title: ON THE FATE OF TRICLOSAN IN HUMANS; url: http://diss.kib.ki.se/2009/978-91-7409-510-4/thesis.pdf; parent_key: DB08604.", + "ref-id: L2091; title: Zinc Toxicity in Humans; url: https://pdfs.semanticscholar.org/a9e2/8321ae506e646f32ce59d87b7589851aa7e4.pdf; parent_key: DB11248.", + "ref-id: L2885; title: Amino Acid Sequence of Phospholipase AZ-a! from the Venom of Crotalus adamanteus; url: http://www.jbc.org/content/252/14/4913.full.pdf; parent_key: DB13893.", + "ref-id: L5843; title: Bipolar Disorders and Lithium: Pharmacokinetics, Pharmacodynamics, Therapeutic Effects and Indications of Lithium: Review of Articles; url: http://austinpublishinggroup.com/psychiatry-behavioral-sciences/fulltext/ajpbs-v3-id1053.php; parent_key: DB14509.", + "ref-id: L2736; title: Hexylresorcinol: Providing Skin Benefits by Modulating Multiple Molecular Targets; url: https://www.researchgate.net/publication/283776287_Hexylresorcinol_Providing_Skin_Benefits_by_Modulating_Multiple_Molecular_Targets; parent_key: DB11254.", + "ref-id: L5983; title: Canadian Mental Health Association; url: https://cmha.ca/documents/anxiety-disorders; parent_key: DB01142.", + "ref-id: L2201; title: Emerging options for the management of scorpion stings; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401053/; parent_key: DB13905.", + "ref-id: L1516; title: Low dose pipamperone in treatment mood disorders; url: https://patents.google.com/patent/WO2010112529A1; parent_key: DB09286.", + "ref-id: L2594; title: List of Permitted Emulsifying, Gelling, Stabilizing or Thickening Agents (Lists of Permitted Food Additives); url: https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/food-additives/lists-permitted/4-emulsifying-gelling-stabilizing-thickening-agents.html; parent_key: DB13707.", + "ref-id: L775; title: Dailymed L-Methyl-MC-NAC Tablets; url: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=177531; parent_key: DB11256.", + "ref-id: L5980; title: American Psychiatric Association; url: https://www.psychiatry.org/patients-families/depression/what-is-depression; parent_key: DB01142.", + "ref-id: L2715; title: FDA Listing of Propionic Acid; url: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1081; parent_key: DB03766.", + "ref-id: L5590; title: Questions and Answers: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist); url: https://www.fda.gov/drugs/drugsafety/ucm334041.htm; parent_key: DB00425.", + "ref-id: L1352; title: APA: Practice Guideline for the Treatment of Patients with Bipolar Disorder Second Edition; url: https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar.pdf; parent_key: DB00458.", + "ref-id: L2107; title: Zinc homeostasis in humans; url: https://academic.oup.com/jn/article/130/5/1360S/4686372; parent_key: DB01593.", + "ref-id: L852; title: American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017.; url: http://hcvguidelines.org/full-report-view; parent_key: DB11574.", + "ref-id: L5936; title: Canadian Mental Health Association; url: https://cmha.ca/mental-health/understanding-mental-illness/schizophrenia; parent_key: DB00334.", + "ref-id: L933; title: European Medicines Agency (EMA): TEYSUNO (tegafur/gimeracil/oteracil) Summary of Product Characteristics; url: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001242/WC500104415.pdf; parent_key: DB03209.", + "ref-id: L2714; title: Novartis receives FDA approval of Tafinlar® + Mekinist® for adjuvant treatment of BRAF V600-mutant melanoma; url: https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-tafinlarr-mekinistr-adjuvant-treatment-braf-v600-mutant-melanoma; parent_key: DB08912.", + "ref-id: L1764; title: Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489477/; parent_key: DB11090.", + "ref-id: L2089; title: Absorption and metabolism of oral zinc gluconate in humans in fasting state, during, and after a meal; url: https://link.springer.com/article/10.1007/BF02784604; parent_key: DB11248.", + "ref-id: L1422; title: Nitazoxanide: A New Thiazolide Antiparasitic Agent; url: https://academic.oup.com/cid/article/40/8/1173/320667; parent_key: DB00507.", + "ref-id: L2091; title: Zinc Toxicity in Humans; url: https://pdfs.semanticscholar.org/a9e2/8321ae506e646f32ce59d87b7589851aa7e4.pdf; parent_key: DB14487.", + "ref-id: L2213; title: The emerging role of zinc transporters; url: https://www.nature.com/articles/sigtrans201729; parent_key: DB14487." + ] + }, + { + "example_idx": 95, + "anchor_id": 3925343160625888881, + "positive_id": 2108365686329947448, + "join_paths": [ + [ + 0, + 7, + 0.26953125 + ], + [ + 0, + 18, + 0.26953125 + ], + [ + 4, + 18, + 0.1875 + ], + [ + 0, + 6, + 0.1826171875 + ], + [ + 4, + 7, + 0.1708984375 + ] + ], + "rows": [ + "β-Hexosaminidases (β-hex) are a group of glycosyl hydrolase isozymes that break down neutral and sialylated glycosphingolipids in the lysosomes, thereby preventing their buildup in neuronal cells.", + "Some mutants of β-hex have decreased folding stability that results in adult-onset forms of lysosomal storage diseases.", + "However, prevention of the harmful accumulation of glycolipids only requires 10% of wild-type activity.", + "Pyrimethamine (PYR) is a potential pharmacological chaperone that works by stabilizing these mutant enzymes sufficiently to allow more β-hex to arrive in the lysosome, where it can carry out its function.", + "An X-ray structure of the complex between human β-hexosaminidase B (HexB) and PYR has been determined to 2.8 Å. PYR binds to the active site of HexB where several favorable van der Waals contacts and hydrogen bonds are introduced.", + "Small adjustments of the enzyme structure are required to accommodate the ligand, and details of the inhibition and stabilization properties of PYR are discussed.", + "Catalytic Domain\nCrystallography, X-Ray\nHumans\nHydrogen Bonding\nIsoenzymes\nModels, Molecular\nMolecular Structure\nProtein Binding\nProtein Subunits\nPyrimethamine\nbeta-N-Acetylhexosaminidases" + ], + "sentences": [ + "id: BE0002837; name: Hydrolase; organism: Alicyclobacillus acidocaldarius; known_action: unknown; parent_key: DB02776.", + "id: BE0001097; name: Mitogen-activated protein kinase 10; organism: Humans; known_action: unknown; parent_key: DB01782.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; parent_key: DB00807.", + "id: BE0009062; name: Keratin, type I cytoskeletal 10; organism: Humans; known_action: unknown; position: 152; parent_key: DB09130.", + "id: BE0008990; name: Alpha-hemoglobin-stabilizing protein; organism: Humans; known_action: unknown; position: 4; parent_key: DB14489.", + "id: BE0009352; name: Lung epithelial cells; organism: Humans; known_action: unknown; position: 9; parent_key: DB14001.", + "id: BE0000876; name: Lysosomal alpha-glucosidase; organism: Humans; known_action: yes; position: 1; parent_key: DB00491.", + "id: BE0001153; name: Beta-hexosaminidase subunit beta; organism: Humans; known_action: unknown; parent_key: DB02813.", + "id: BE0009373; name: Skin epithelial cells; organism: Humans; known_action: yes; position: 1; parent_key: DB11185.", + "id: BE0001097; name: Mitogen-activated protein kinase 10; organism: Humans; known_action: unknown; position: 2; parent_key: DB07010.", + "id: BE0003894; name: Beta-lactamase TEM; organism: Escherichia coli; known_action: unknown; position: 1; parent_key: DB04430.", + "id: BE0009541; name: Serine/threonine-protein kinase 10; organism: Humans; known_action: unknown; position: 296; parent_key: DB12010.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; parent_key: DB00961.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB00721.", + "id: BE0003072; name: Hydrolase; organism: Streptomyces olivaceoviridis; known_action: unknown; parent_key: DB04465.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB01161.", + "id: BE0003291; name: Chaperone protein ClpB; organism: Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579); known_action: unknown; parent_key: DB04395.", + "id: BE0003848; name: Nuclear receptor subfamily 1 group I member 3; organism: Humans; known_action: unknown; position: 26; parent_key: DB01026.", + "id: BE0003869; name: Beta-hexosaminidase; organism: Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961); known_action: unknown; position: 1; parent_key: DB08704.", + "id: BE0000864; name: Voltage-dependent T-type calcium channel subunit alpha-1H; organism: Humans; known_action: yes; position: 7; parent_key: DB00568.", + "id: BE0004849; name: Hydrogen ions; known_action: yes; position: 1; parent_key: DB11098.", + "id: BE0008990; name: Alpha-hemoglobin-stabilizing protein; organism: Humans; known_action: unknown; position: 4; parent_key: DB14490.", + "id: BE0003184; name: Hydrolase; organism: Thermus sp.; known_action: unknown; parent_key: DB03801.", + "id: BE0008990; name: Alpha-hemoglobin-stabilizing protein; organism: Humans; known_action: unknown; position: 4; parent_key: DB14488.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; parent_key: DB00296.", + "id: BE0001097; name: Mitogen-activated protein kinase 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB08011.", + "id: BE0008990; name: Alpha-hemoglobin-stabilizing protein; organism: Humans; known_action: unknown; position: 4; parent_key: DB14501.", + "id: BE0001097; name: Mitogen-activated protein kinase 10; organism: Humans; known_action: unknown; parent_key: DB03623.", + "id: BE0001277; name: Serine/threonine-protein kinase pim-1; organism: Humans; known_action: unknown; parent_key: DB02010.", + "id: BE0002699; name: Glycosyl transferase; organism: Neisseria meningitidis; known_action: unknown; parent_key: DB02976.", + "id: BE0000214; name: Histo-blood group ABO system transferase; organism: Humans; known_action: unknown; position: 1; parent_key: DB07357.", + "id: BE0001097; name: Mitogen-activated protein kinase 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB08015.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; position: 1; parent_key: DB00297.", + "id: BE0001756; name: GDP-mannose mannosyl hydrolase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04315.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; parent_key: DB01086.", + "id: BE0000752; name: Sodium/hydrogen exchanger 1; organism: Humans; known_action: unknown; parent_key: DB02624.", + "id: BE0001097; name: Mitogen-activated protein kinase 10; organism: Humans; known_action: unknown; parent_key: DB03084.", + "id: BE0009757; name: Sodium/hydrogen exchanger 3; organism: Humans; known_action: yes; position: 1; parent_key: DB11761.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; parent_key: DB00527.", + "id: BE0003777; name: Beta-2-microglobulin; organism: Humans; known_action: unknown; position: 94; parent_key: DB09130.", + "id: BE0001689; name: Putative regulator of ribonuclease activity; organism: Mycobacterium tuberculosis; known_action: unknown; parent_key: DB04343.", + "id: BE0009221; name: Chaperone, putative; organism: Plasmodium falciparum (isolate 3D7); known_action: unknown; position: 140; parent_key: DB11638.", + "id: BE0000236; name: Neutral amino acid transporter B(0); organism: Humans; known_action: unknown; parent_key: DB00174.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; position: 7; parent_key: DB06262.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: unknown; position: 9; parent_key: DB01221.", + "id: BE0001097; name: Mitogen-activated protein kinase 10; organism: Humans; known_action: unknown; position: 1; parent_key: DB08025.", + "id: BE0003072; name: Hydrolase; organism: Streptomyces olivaceoviridis; known_action: unknown; parent_key: DB03389.", + "id: BE0004878; name: Nuclear factor of activated T-cells, cytoplasmic 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00852.", + "id: BE0003858; name: Cytochrome b-c1 complex subunit Rieske, mitochondrial; organism: Humans; known_action: unknown; position: 7; parent_key: DB04799.", + "id: BE0001097; name: Mitogen-activated protein kinase 10; organism: Humans; known_action: unknown; position: 192; parent_key: DB12010." + ] + }, + { + "example_idx": 96, + "anchor_id": 17145101548056232275, + "positive_id": 14870405892677387218, + "join_paths": [ + [ + 0, + 18, + 0.337890625 + ], + [ + 0, + 39, + 0.330078125 + ], + [ + 0, + 3, + 0.318359375 + ], + [ + 0, + 34, + 0.310546875 + ], + [ + 0, + 15, + 0.30078125 + ] + ], + "rows": [ + "Sildenafil is a potent and selective inhibitor of the type 5 cGMP (cyclic guanosine 3',5'-monophosphate)-specific phosphodiesterase that is used clinically to treat erectile dysfunction and pulmonary arterial hypertension.", + "Here, we report that sildenafil has differential effects on cell surface ABC transporters such as ABCB1, ABCC1, and ABCG2 that modulate intracompartmental and intracellular concentrations of chemotherapeutic drugs.", + "In ABCB1-overexpressing cells, nontoxic doses of sildenafil inhibited resistance and increased the effective intracellular concentration of ABCB1 substrate drugs such as paclitaxel.", + "Similarly, in ABCG2-overexpressing cells, sildenafil inhibited resistance to ABCG2 substrate anticancer drugs, for example, increasing the effective intracellular concentration of mitoxantrone or the fluorescent compound BODIPY-prazosin.", + "Sildenafil also moderately inhibited the transport of E(2)17βG and methotrexate by the ABCG2 transporter.", + "Mechanistic investigations revealed that sildenafil stimulated ABCB1 ATPase activity and inhibited photolabeling of ABCB1 with [(125)I]-iodoarylazidoprazosin (IAAP), whereas it only slightly stimulated ABCG2 ATPase activity and inhibited photolabeling of ABCG2 with [(125)I]-IAAP.", + "In contrast, sildenafil did not alter the sensitivity of parental, ABCB1-, or ABCG2-overexpressing cells to non-ABCB1 and non-ABCG2 substrate drugs, nor did sildenafil affect the function of another ABC drug transporter, ABCC1.", + "Homology modeling predicted the binding conformation of sildenafil within the large cavity of the transmembrane region of ABCB1.", + "Overall, we found that sildenafil inhibits the transporter function of ABCB1 and ABCG2, with a stronger effect on ABCB1.", + "Our findings suggest a possible strategy to enhance the distribution and potentially the activity of anticancer drugs by jointly using a clinically approved drug with known side effects and drug-drug interactions.", + "ATP Binding Cassette Transporter, Subfamily G, Member 2\nATP-Binding Cassette Transporters\nAdenosine Triphosphatases\nBoron Compounds\nCarcinoma, Squamous Cell\nCell Line, Tumor\nDrug Resistance, Neoplasm\nDrug Synergism\nHumans\nKB Cells\nMethotrexate\nMitoxantrone\nModels, Molecular\nMultidrug Resistance-Associated Proteins\nNeoplasm Proteins\nPaclitaxel\nPiperazines\nPrazosin\nPurines\nSildenafil Citrate\nSulfones" + ], + "sentences": [ + "name: Apo-methotrexate; ingredients: Methotrexate; parent_key: DB00563.", + "name: Jayjun Real Water Brightening Black Mask Step3 Real Water Brightening Black Mask; ingredients: Adenosine + Allantoin + Glycerin + Nicotinamide; parent_key: DB09462.", + "name: Apo-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Sildenafil Citrate; ingredients: Sildenafil; parent_key: DB00203.", + "name: Vaxelis; ingredients: Bordetella pertussis filamentous hemagglutinin antigen (formaldehyde inactivated) + Bordetella pertussis fimbriae 2/3 antigen + Bordetella pertussis pertactin antigen + Bordetella pertussis toxoid antigen (glutaraldehyde inactivated) + Clostridium tetani toxoid antigen (formaldehyde inactivated) + Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) + Haemophilus influenzae type B capsular polysaccharide meningococcal outer membrane protein conjugate antigen + Hepatitis B Vaccine (Recombinant) + Poliovirus type 1 antigen (formaldehyde inactivated) + Poliovirus type 2 antigen (formaldehyde inactivated) + Poliovirus type 3 antigen (formaldehyde inactivated); parent_key: DB10342.", + "name: Methotrexate-liq Im IV Iar Int Ivr 25mg/ml; ingredients: Methotrexate; parent_key: DB00563.", + "name: Dom-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Apo-sildenafil R; ingredients: Sildenafil; parent_key: DB00203.", + "name: MIRACLETOX Time Rewind Advanced Meso Tox; ingredients: Adenosine + Nicotinamide; parent_key: DB00640.", + "name: Metoject Subcutaneous; ingredients: Methotrexate; parent_key: DB00563.", + "name: Methotrexate Sodium; ingredients: Methotrexate; parent_key: DB00563.", + "name: Rheumatrex-tab 2.5mg; ingredients: Methotrexate; parent_key: DB00563.", + "name: Cpd Adenine Cpda 1; ingredients: Adenine + Citric acid + Dextrose, unspecified form + Sodium citrate + Sodium phosphate, monobasic; parent_key: DB00173.", + "name: Propolis 80; ingredients: Adenosine + Nicotinamide + Propolis wax; parent_key: DB11355.", + "name: Centella 80 Eye; ingredients: Adenosine + Nicotinamide; parent_key: DB00640.", + "name: Sildenafil Ratiopharm; ingredients: Sildenafil; parent_key: DB00203.", + "name: PMS-sildenafil R; ingredients: Sildenafil; parent_key: DB00203.", + "name: Revatio; ingredients: Sildenafil; parent_key: DB00203.", + "name: Sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: TERUFLEX Blood Bag System Anticoagulant Citrate Phosphate Dextrose (CPD) AND OPTISOL Red Cell Preservative; ingredients: Adenine + Citric acid + D-glucose + D-glucose + Mannitol + Sodium chloride + Sodium citrate + Sodium phosphate, monobasic, unspecified form; parent_key: DB14503.", + "name: Mitoxantrone; ingredients: Mitoxantrone; parent_key: DB01204.", + "name: Ipg-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Saffron Edition Mask Sheet; ingredients: Adenosine + Nicotinamide; parent_key: DB00640.", + "name: Myl-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Foltabs Prenatal; ingredients: Ascorbic acid + Calcium citrate + Cholecalciferol + Cupric oxide + DL-alpha tocopheryl acetate + Docusate + Ferrous gluconate + Folic acid + Iron + Nicotinamide + Potassium Iodide + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB00169.", + "name: Methotrexate Sodium Inj 25.0mg/ml; ingredients: Methotrexate; parent_key: DB00563.", + "name: Methotrexate Injection USP; ingredients: Methotrexate; parent_key: DB00563.", + "name: Gd-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Act Sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: White truffle Anti Wrinkle; ingredients: Adenosine + Glycerin + Nicotinamide; parent_key: DB02701.", + "name: Methotrexate Tablets, USP; ingredients: Methotrexate; parent_key: DB00563.", + "name: Ag-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Teva-sildenafil R; ingredients: Sildenafil; parent_key: DB00203.", + "name: Ratio-methotrexate Sodium; ingredients: Methotrexate; parent_key: DB00563.", + "name: Sildenafil R; ingredients: Sildenafil; parent_key: DB00203.", + "name: Methotrexate Sodium Inj 25mg/ml; ingredients: Methotrexate; parent_key: DB00563.", + "name: Methotrexate Dbl Inj 10mg/ml; ingredients: Methotrexate; parent_key: DB00563.", + "name: Methotrexate PF/sa Injection; ingredients: Methotrexate; parent_key: DB00563.", + "name: Jamp-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Sildenafil Tablets; ingredients: Sildenafil; parent_key: DB00203.", + "name: Viagra; ingredients: Sildenafil; parent_key: DB00203.", + "name: Methotrexate Tab 2.5mg USP; ingredients: Methotrexate; parent_key: DB00563.", + "name: Sildenafil Teva; ingredients: Sildenafil; parent_key: DB00203.", + "name: Methotrexate Sodium Injection; ingredients: Methotrexate; parent_key: DB00563.", + "name: Nra-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Jamp-sildenafil R; ingredients: Sildenafil; parent_key: DB00203.", + "name: RediTrex; ingredients: Methotrexate; parent_key: DB00563.", + "name: Methotrexate Sodium Injection USP; ingredients: Methotrexate; parent_key: DB00563.", + "name: Riva-sildenafil; ingredients: Sildenafil; parent_key: DB00203.", + "name: Methotrexate Dbl Inj 2.5mg/ml; ingredients: Methotrexate; parent_key: DB00563." + ] + }, + { + "example_idx": 97, + "anchor_id": 10374103793540834644, + "positive_id": 11024640373049550181, + "join_paths": [ + [ + 8, + 7, + 0.203125 + ], + [ + 8, + 47, + 0.203125 + ], + [ + 8, + 1, + 0.2021484375 + ], + [ + 8, + 23, + 0.2021484375 + ], + [ + 8, + 18, + 0.201171875 + ] + ], + "rows": [ + "The hormonal and biochemical effects of danazol (600 mg a day) and high-dose medroxyprogesterone acetate (MPA; 100 mg a day) were studied in a placebo-controlled, 6-month trial.", + "Serum gonadotrophins and prolactin levels did not change during danazol and MPA treatments, whereas oestradiol and progesterone levels decreased significantly in relation to placebo without any difference between danazol and MPA.", + "Both drugs significantly suppressed the sex hormone-binding globulin level (SHBG), and consequently, the free-androgen index (serum total testosterone nmol/l per SHBG nmol/l x 100) as compared with placebo, the effect of danazol being significantly stronger than that of MPA.", + "Danazol, but not MPA, significantly increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and haemoglobin levels, and also thrombocyte counts, whereas MPA, but not danazol, increased the serum concentration of albumin in relation to placebo.", + "Serum total bilirubin, conjugated bilirubin, gamma-glutamyl transferase, creatinine, alkaline phosphatase, sodium and potassium levels and leucocyte counts remained unchanged during both treatments.", + "Danazol and high-dose MPA did not differ from each other in their ovarian and anterior pituitary effects, while the increase in androgenic activity induced by danazol was greater than that achieved with MPA.", + "Danazol also had more biochemical effects than MPA.", + "It interfered with the functions of the liver and the production of thrombocytes and haemoglobin, whereas MPA affected only albumin synthesis/release.", + "Adult\nAlanine Transaminase\nAndrogens\nAspartate Aminotransferases\nClinical Trials as Topic\nDanazol\nEndometriosis\nEstradiol\nFemale\nFollicle Stimulating Hormone\nHemoglobins\nHormones\nHumans\nLuteinizing Hormone\nMedroxyprogesterone\nMedroxyprogesterone Acetate\nPlatelet Count\nPregnadienes\nProspective Studies\nSex Hormone-Binding Globulin\nTestosterone" + ], + "sentences": [ + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB04574.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; parent_key: DB02901.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 7; parent_key: DB06710.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 3; parent_key: DB14518.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB13955.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 1; parent_key: DB03585.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; parent_key: DB02342.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB14542.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 23; parent_key: DB00286.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB14538.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB00783.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 10; parent_key: DB05294.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 1; parent_key: DB13951.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 16; parent_key: DB00624.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB14541.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00648.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 3; parent_key: DB00294.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB13953.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB15690.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB14543.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 10; parent_key: DB00957.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 1; parent_key: DB11590.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: yes; position: 6; parent_key: DB01406.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB13954.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 6; parent_key: DB13943.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; parent_key: DB03926.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB14539.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; parent_key: DB03882.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 6; parent_key: DB13946.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 12; parent_key: DB00717.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; parent_key: DB00858.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 4; parent_key: DB06282.", + "id: BE0001179; name: Phosphatidylethanolamine-binding protein 1; organism: Humans; known_action: no; position: 2; parent_key: DB09568.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB13952.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 5; parent_key: DB00304.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 6; parent_key: DB13944.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 2; parent_key: DB00741.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB13956.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 7; parent_key: DB06716.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB14544.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 28; parent_key: DB01026.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 12; parent_key: DB01039.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 4; parent_key: DB01185.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 1; parent_key: DB00414.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 3; parent_key: DB09124.", + "id: BE0000530; name: Serum albumin; organism: Humans; known_action: unknown; position: 7; parent_key: DB01124.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; parent_key: DB06412.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 17; parent_key: DB00977.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: no; position: 7; parent_key: DB01420.", + "id: BE0000685; name: Sex hormone-binding globulin; organism: Humans; known_action: unknown; position: 3; parent_key: DB14540." + ] + }, + { + "example_idx": 98, + "anchor_id": 8638172886919647516, + "positive_id": 17394743925684544627, + "join_paths": [ + [ + 0, + 12, + 0.2294921875 + ], + [ + 0, + 42, + 0.228515625 + ], + [ + 1, + 42, + 0.2138671875 + ], + [ + 13, + 26, + 0.2109375 + ], + [ + 1, + 12, + 0.201171875 + ] + ], + "rows": [ + "Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells.", + "Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature.", + "For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosinolates and phenylthiocarbamide (PTC).", + "While many substances are known to activate TAS2Rs, only one inhibitor that specifically blocks bitter receptor activation has been described.", + "Here, we describe a new inhibitor of bitter taste receptors, p-(dipropylsulfamoyl)benzoic acid (probenecid), that acts on a subset of TAS2Rs and inhibits through a novel, allosteric mechanism of action.", + "Probenecid is an FDA-approved inhibitor of the Multidrug Resistance Protein 1 (MRP1) transporter and is clinically used to treat gout in humans.", + "Probenecid is also commonly used to enhance cellular signals in GPCR calcium mobilization assays.", + "We show that probenecid specifically inhibits the cellular response mediated by the bitter taste receptor hTAS2R16 and provide molecular and pharmacological evidence for direct interaction with this GPCR using a non-competitive (allosteric) mechanism.", + "Through a comprehensive analysis of hTAS2R16 point mutants, we define amino acid residues involved in the probenecid interaction that result in decreased sensitivity to probenecid while maintaining normal responses to salicin.", + "Probenecid inhibits hTAS2R16, hTAS2R38, and hTAS2R43, but does not inhibit the bitter receptor hTAS2R31 or non-TAS2R GPCRs.", + "Additionally, structurally unrelated MRP1 inhibitors, such as indomethacin, fail to inhibit hTAS2R16 function.", + "Finally, we demonstrate that the inhibitory activity of probenecid in cellular experiments translates to inhibition of bitter taste perception of salicin in humans.", + "This work identifies probenecid as a pharmacological tool for understanding the cell biology of bitter taste and as a lead for the development of broad specificity bitter blockers to improve nutrition and medical compliance.", + "Benzyl Alcohols\nCCR5 Receptor Antagonists\nGlucosides\nHEK293 Cells\nHumans\nMultidrug Resistance-Associated Proteins\nProbenecid\nReceptors, CCR5\nReceptors, CXCR4\nReceptors, G-Protein-Coupled\nSignal Transduction" + ], + "sentences": [ + "id: BE0005562; name: G-protein coupled receptor 35; organism: Humans; known_action: unknown; position: 12; parent_key: DB00695.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09304.", + "id: BE0005788; name: G-protein coupled bile acid receptor 1; organism: Humans; known_action: unknown; position: 36; parent_key: DB02659.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 4; parent_key: DB08073.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 3; parent_key: DB09286.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB06959.", + "id: BE0001172; name: RAC-beta serine/threonine-protein kinase; organism: Humans; known_action: unknown; position: 1; parent_key: DB08073.", + "id: BE0005562; name: G-protein coupled receptor 35; organism: Humans; known_action: unknown; position: 2; parent_key: DB11937.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: unknown; position: 13; parent_key: DB00715.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB07857.", + "id: BE0000279; name: 30S ribosomal protein S12; organism: Escherichia coli (strain K12); known_action: yes; position: 1; parent_key: DB04729.", + "id: BE0005802; name: G-protein coupled receptor 55; organism: Humans; known_action: yes; position: 3; parent_key: DB11755.", + "id: BE0000395; name: Taste receptor type 1 member 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB02772.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB07204.", + "id: BE0005510; name: Probable G-protein coupled receptor 133; organism: Humans; known_action: unknown; position: 2; parent_key: DB12637.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB09304.", + "id: BE0000089; name: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB08114.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 9; parent_key: DB00490.", + "id: BE0002082; name: Sodium channel protein type 3 subunit alpha; organism: Humans; known_action: yes; position: 3; parent_key: DB00909.", + "id: BE0000846; name: T-lymphocyte activation antigen CD86; organism: Humans; known_action: unknown; position: 5; parent_key: DB11752.", + "id: BE0000405; name: Muscarinic acetylcholine receptor M4; organism: Humans; known_action: unknown; position: 2; parent_key: DB06702.", + "id: BE0003624; name: Penicillin-binding protein 2B; organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6); known_action: yes; position: 3; parent_key: DB00607.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 6; parent_key: DB08231.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 16; parent_key: DB00193.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 8; parent_key: DB00715.", + "id: BE0003639; name: Multidrug resistance-associated protein 5; organism: Humans; known_action: unknown; position: 7; parent_key: DB14635.", + "id: BE0004808; name: Lead; organism: Humans; known_action: unknown; position: 1; parent_key: DB14598.", + "id: BE0004141; name: D-amino-acid oxidase; organism: Humans; known_action: unknown; parent_key: DB03225.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB01049.", + "id: BE0009533; name: Receptor-interacting serine/threonine-protein kinase 4; organism: Humans; known_action: unknown; position: 282; parent_key: DB12010.", + "id: BE0004060; name: Multi-sensor signal transduction histidine kinase; organism: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099); known_action: unknown; position: 2; parent_key: DB02731.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB09204.", + "id: BE0009167; name: Multidrug resistance protein; organism: Plasmodium falciparum (isolate FC27 / Papua New Guinea); known_action: unknown; position: 84; parent_key: DB11638.", + "id: BE0000293; name: Vasopressin V2 receptor; organism: Humans; known_action: yes; parent_key: DB00872.", + "id: BE0000515; name: Melatonin receptor type 1A; organism: Humans; known_action: yes; parent_key: DB00980.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB00598.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB08569.", + "id: BE0005802; name: G-protein coupled receptor 55; organism: Humans; known_action: unknown; position: 1; parent_key: DB06155.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB09194.", + "id: BE0004262; name: D-Amino acid amidase; organism: Ochrobactrum anthropi; known_action: unknown; position: 3; parent_key: DB04029.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB06678.", + "id: BE0009016; name: Taste receptor type 2 member 16; organism: Humans; known_action: unknown; position: 25; parent_key: DB01032.", + "id: BE0001817; name: Acriflavine resistance protein B; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04209.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09194.", + "id: BE0001288; name: Triggering receptor expressed on myeloid cells 1; organism: Humans; known_action: unknown; parent_key: DB01694.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: no; position: 6; parent_key: DB00243.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB07876.", + "id: BE0000486; name: Sodium-dependent noradrenaline transporter; organism: Humans; known_action: yes; position: 6; parent_key: DB09225.", + "id: BE0003446; name: G-protein coupled estrogen receptor 1; organism: Humans; known_action: unknown; parent_key: DB05939." + ] + }, + { + "example_idx": 99, + "anchor_id": 16906036764996395213, + "positive_id": 13751514602655870616, + "join_paths": [ + [ + 4, + 43, + 0.33203125 + ], + [ + 4, + 13, + 0.3046875 + ], + [ + 4, + 33, + 0.296875 + ], + [ + 4, + 3, + 0.29296875 + ], + [ + 4, + 15, + 0.291015625 + ] + ], + "rows": [ + "Serum total and free fraction of thyroxine and triiodothyronine and urinary losses of unconjugated hormones in normal subjects and in patients treated long-term with therapeutic doses of phenytoin have been measured.", + "Decreases in serum total hormone concentrations with increased free fractions and resultant significant increase in the concentration of free thyroxine but not triiodothyronine were apparent in phenytoin-treated subjects.", + "However, serum free hormone concentrations remained within the euthyroid range.", + "These changes in serum free hormone concentration were reflected by an increased urinary loss of unconjugated thyroxine, but normal excretion of unconjugated triiodothyronine.", + "Phenytoin in therapeutic doses displaces thyroxine and to a lesser extent, triiodothyronine from binding proteins in serum and thus increases peripheral clearance of thyroid hormones.", + "Adult\nAnticonvulsants\nFemale\nHumans\nMale\nMiddle Aged\nPhenytoin\nThyroid Gland\nThyroid Hormones\nYoung Adult" + ], + "sentences": [ + "name: Repronex; ingredients: Follitropin + Luteinizing hormone; parent_key: DB14741.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14192.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14184.", + "name: Phenytoin Sodium Injection USP; ingredients: Phenytoin; parent_key: DB00252.", + "name: NATPARA (parathyroid hormone); ingredients: Parathyroid hormone; parent_key: DB05829.", + "name: Dilantin Infatabs; ingredients: Phenytoin; parent_key: DB00252.", + "name: Preotact; ingredients: Parathyroid hormone; parent_key: DB05829.", + "name: Dilantin; ingredients: Phenytoin; parent_key: DB00252.", + "name: Dilantin-30 Suspension; ingredients: Phenytoin; parent_key: DB00252.", + "name: Thyroid Tab 60mg; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Hemorro-dol Sup; ingredients: Balsam of Peru + Belladonna + Benzocaine + Bismuth subcarbonate + Bismuth subnitrate + Boric acid + Ephedrine + Zinc oxide; parent_key: DB11482.", + "name: Dilantin W Phenobarbital 30mg Cap; ingredients: Phenobarbital + Phenytoin; parent_key: DB00252.", + "name: Armour Thyroid; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Phenytoin Sodium; ingredients: Phenytoin; parent_key: DB00252.", + "name: Menopur; ingredients: Follitropin + Luteinizing hormone; parent_key: DB09153.", + "name: Phenytek; ingredients: Phenytoin; parent_key: DB00252.", + "name: Dilantin Kapseals; ingredients: Phenytoin; parent_key: DB00252.", + "name: Thyroid; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Extended Phenytoin Sodium; ingredients: Phenytoin; parent_key: DB00252.", + "name: Membraneblue; ingredients: Trypan blue free acid; parent_key: DB09158.", + "name: Pergonal 75 I.U.; ingredients: Follitropin + Luteinizing hormone; parent_key: DB14741.", + "name: Dilantin Inj 50mg/ml; ingredients: Phenytoin; parent_key: DB00252.", + "name: Visionblue; ingredients: Trypan blue free acid; parent_key: DB09158.", + "name: Venelex; ingredients: Balsam of Peru + Castor oil; parent_key: DB11482.", + "name: D.O.R.C. Vision Blue; ingredients: Trypan blue free acid; parent_key: DB09158.", + "name: Taro-phenytoin; ingredients: Phenytoin; parent_key: DB00252.", + "name: Thyroid, Porcine; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Armour thyroid; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Erfa Thyroid; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Phenytoin ER; ingredients: Phenytoin; parent_key: DB00252.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14190.", + "name: Menopur; ingredients: Follitropin + Luteinizing hormone; parent_key: DB14741.", + "name: Octaplas; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Phenytoin Infatabs; ingredients: Phenytoin; parent_key: DB00252.", + "name: Stroke II Synergy; ingredients: Balsam of Peru + Levomenthol; parent_key: DB00825.", + "name: Phenytoin Sodium Extended; ingredients: Phenytoin; parent_key: DB00252.", + "name: In-111 DTPA; ingredients: Indium In-111 pentetate; parent_key: DB09425.", + "name: Nature-Throid; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Thyroid Tab 30mg; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Dilantin-125; ingredients: Phenytoin; parent_key: DB00252.", + "name: Repronex; ingredients: Follitropin + Luteinizing hormone; parent_key: DB00066.", + "name: Phenytoin Sodium Injection, USP; ingredients: Phenytoin; parent_key: DB00252.", + "name: Phenytoin Soidum Injection USP; ingredients: Phenytoin; parent_key: DB00252.", + "name: Phenytoin; ingredients: Phenytoin; parent_key: DB00252.", + "name: Atopic Healer Synergy; ingredients: Balsam of Peru + Cocoa butter; parent_key: DB11086.", + "name: Thyroid Tab 125mg; ingredients: Thyroid, porcine; parent_key: DB09100.", + "name: Pergonal 75 I.U.; ingredients: Follitropin + Luteinizing hormone; parent_key: DB00066.", + "name: Dilantin-125 Suspension; ingredients: Phenytoin; parent_key: DB00252.", + "name: Novo-phenytoin Cap 100mg; ingredients: Phenytoin; parent_key: DB00252.", + "name: Menopur; ingredients: Follitropin + Luteinizing hormone; parent_key: DB00066." + ] + }, + { + "example_idx": 100, + "anchor_id": 8591270496136243256, + "positive_id": 15349598884333728070, + "join_paths": [ + [ + 10, + 14, + 0.1865234375 + ], + [ + 10, + 10, + 0.185546875 + ], + [ + 10, + 16, + 0.185546875 + ], + [ + 10, + 17, + 0.185546875 + ], + [ + 10, + 0, + 0.1845703125 + ] + ], + "rows": [ + "INTRODUCTION: Treatment with dopamine agonists in patients with prolactin (PRL) adenomas and Parkinson's disease is associated with central side effects.", + "Central side effects may depend on a substance's ability to pass the blood-brain barrier, which can be actively controlled by transporter molecules such as the P-glycoprotein (P-gp) encoded by the ABCB1 gene.", + "MATERIALS AND METHODS: We aimed to determine whether cabergoline is transported by the P-gp and whether polymorphisms of its encoding ABCB1 gene predict central side effects of cabergoline therapy in patients with PRL adenomas.", + "i) In an experimental mouse model lacking the homologues of the human ABCB1 gene (Abcb1ab double knockout mouse model), we examined whether cabergoline is a substrate of the P-gp using eight mutant and eight wild-type mice.", + "ii) In a human case-control study including 79 patients with PRL adenomas treated with cabergoline at the Max Planck Institute of Psychiatry in Munich, we investigated the association of four selected ABCB1 gene single nucleotide polymorphisms (SNPs) (rs1045642, rs2032582, rs2032583 and rs2235015), with the occurrence of central side effects under cabergoline therapy.", + "RESULTS: i) In the experimental mouse model, we observed that brain concentrations of cabergoline were tenfold higher in the mutant mice compared with their wild-type littermates, implying that cabergoline is indeed a substrate of the transporter P-gp at the blood-brain barrier level.", + "ii) In the human study, we observed significant negative associations under cabergoline for the C-carriers and heterozygous CT individuals of SNP rs1045642 with two central side effects (frequency of fatigue and sleep disorders) and for the G-carriers of SNP rs2032582 with the enhancement of dizziness.", + "For the SNPs rs2235015 and rs2032583, no associations with central side effects under cabergoline were found.", + "DISCUSSION: This is the first study demonstrating that individual ABCB1 gene polymorphisms, reflecting a different expression and function of the P-gp, could predict the occurrence of central side effects under cabergoline.", + "Our findings can be viewed as a step into personalised therapy in PRL adenoma patients.", + "ATP Binding Cassette Transporter, Subfamily D, Member 1\nATP-Binding Cassette Transporters\nAdult\nAged\nAnimals\nAntineoplastic Agents\nCabergoline\nCase-Control Studies\nErgolines\nFatigue\nFemale\nHeadache\nHumans\nMale\nMice\nMice, Knockout\nMiddle Aged\nPituitary Neoplasms\nPolymorphism, Single Nucleotide\nPredictive Value of Tests\nProlactinoma\nTreatment Outcome" + ], + "sentences": [ + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB14541.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 11; parent_key: DB00515.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00655.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB11817.", + "id: BE0000447; name: Solute carrier family 13 member 2; organism: Humans; known_action: no; position: 2; parent_key: DB09154.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 8; parent_key: DB00448.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 8; parent_key: DB06605.", + "id: BE0003647; name: Solute carrier family 22 member 2; organism: Humans; known_action: unknown; position: 10; parent_key: DB00594.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 13; parent_key: DB12267.", + "id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: no; position: 5; parent_key: DB11362.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB08880.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00970.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 20; parent_key: DB00201.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB14543.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 4; parent_key: DB09291.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB01094.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 3; parent_key: DB11952.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 3; parent_key: DB09330.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 23; parent_key: DB14011.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB09038.", + "id: BE0001066; name: Solute carrier family 22 member 6; organism: Humans; known_action: unknown; position: 6; parent_key: DB01147.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 8; parent_key: DB00773.", + "id: BE0002369; name: ATP-binding cassette sub-family B member 5; organism: Humans; known_action: unknown; position: 3; parent_key: DB06263.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 16; parent_key: DB00495.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00958.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB08864.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 6; parent_key: DB09074.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 16; parent_key: DB13943.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 7; parent_key: DB11855.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB00694.", + "id: BE0001069; name: Canalicular multispecific organic anion transporter 1; organism: Humans; known_action: unknown; position: 15; parent_key: DB00481.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB06290.", + "id: BE0001066; name: Solute carrier family 22 member 6; organism: Humans; known_action: unknown; position: 1; parent_key: DB08844.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 11; parent_key: DB11633.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 21; parent_key: DB00286.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00973.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB11827.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 25; parent_key: DB08896.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB13125.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: no; position: 1; parent_key: DB12364.", + "id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB00959.", + "id: BE0000119; name: ATP-binding cassette sub-family A member 1; organism: Humans; known_action: no; position: 8; parent_key: DB11635.", + "id: BE0001066; name: Solute carrier family 22 member 6; organism: Humans; known_action: unknown; position: 5; parent_key: DB00586.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB00470.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 19; parent_key: DB13956.", + "id: BE0000669; name: Monocarboxylate transporter 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB03773.", + "id: BE0002369; name: ATP-binding cassette sub-family B member 5; organism: Humans; known_action: no; position: 9; parent_key: DB11943.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00317.", + "id: BE0000119; name: ATP-binding cassette sub-family A member 1; organism: Humans; known_action: unknown; position: 34; parent_key: DB00675.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 8; parent_key: DB00549." + ] + }, + { + "example_idx": 101, + "anchor_id": 17257331939617767351, + "positive_id": 11491474341878305472, + "join_paths": [ + [ + 6, + 9, + 0.259765625 + ], + [ + 8, + 9, + 0.2490234375 + ], + [ + 6, + 4, + 0.23046875 + ], + [ + 6, + 13, + 0.23046875 + ], + [ + 8, + 4, + 0.2294921875 + ] + ], + "rows": [ + "BACKGROUND AND PURPOSE: Retention of substances from systemic circulation in the brain and testes are limited due to high levels of P-glycoprotein (P-gp) in the luminal membranes of brain and testes capillary endothelial cells.", + "From a clinical perspective, P-gp rapidly extrudes lipophilic therapeutic agents, which then fail to reach efficacious levels.", + "Recent studies have demonstrated that acute administration of selective serotonin reuptake inhibitors (SSRI) can affect P-gp function, in vitro and in vivo.", + "However, little is known concerning the time-course of these effects or the effects of different SSRI in vivo.", + "EXPERIMENTAL APPROACH: The P-gp substrate, tritiated digoxin ([(3)H] digoxin), was co-administered with fluoxetine or sertraline to determine if either compound increased drug accumulation within the brains and testes of mice due to inhibition of P-gp activity.", + "We undertook parallel studies in endothelial cells derived from brain microvessels to determine the dose-response and time-course of effects.", + "KEY RESULTS: In vitro, sertraline resulted in rapid and potent inhibition of P-gp function in brain endothelial cells, as determined by cellular calcein accumulation.", + "In vivo, a biphasic effect was demonstrated.", + "Brain accumulation of [(3)H] digoxin was increased 5 minutes after treatment with sertraline, but by 60 minutes after sertraline treatment, brain accumulation of digoxin was reduced compared to control.", + "By 240 minutes after sertraline treatment brain digoxin accumulation was elevated compared to control.", + "A similar pattern of results was obtained in the testes.", + "There was no significant effect of fluoxetine on P-gp function, in vitro or in vivo.", + "CONCLUSIONS AND IMPLICATIONS: Acute sertraline administration can modulate P-gp activity in the blood-brain barrier and blood-testes barrier.", + "This clearly has implications for the ability of therapeutic agents that are P-gp substrates, to enter the brain when co-administered with SSRI.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAnimals\nBiological Transport\nBlood-Brain Barrier\nBlood-Testis Barrier\nEndothelial Cells\nFluoxetine\nGuinea Pigs\nMale\nMice\nSerotonin Uptake Inhibitors\nSertraline\nTime Factors" + ], + "sentences": [ + "name: Jamp Digoxin; ingredients: Digoxin; parent_key: DB00390.", + "name: Digoxin Injection C.S.D.; ingredients: Digoxin; parent_key: DB00390.", + "name: Teva-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Lanoxin Tab 0.25mg; ingredients: Digoxin; parent_key: DB00390.", + "name: Sertraline Hydrochloride; ingredients: Sertraline; parent_key: DB01104.", + "name: Flucelvax Quadrivalent (multi-dose Vial); ingredients: Influenza A virus A/Singapore/GP1908/2015 IVR-180 (H1N1) antigen (MDCK cell derived, propiolactone inactivated) + Influenza A virus A/Singapore/GP2050/2015 (H3N2) antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Hong Kong/259/2010 antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Utah/9/2014 antigen (MDCK cell derived, propiolactone inactivated); parent_key: DB14464.", + "name: Mint-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Novo-digoxin Tab 0.25mg; ingredients: Digoxin; parent_key: DB00390.", + "name: Lanoxin Tab 0.125mg; ingredients: Digoxin; parent_key: DB00390.", + "name: Sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Pediatric Digoxin Injection C.S.D.; ingredients: Digoxin; parent_key: DB00390.", + "name: Auro-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Lanoxin Inj 0.25mg/ml; ingredients: Digoxin; parent_key: DB00390.", + "name: Sertraline hydrochloride; ingredients: Sertraline; parent_key: DB01104.", + "name: Digox; ingredients: Digoxin; parent_key: DB00390.", + "name: Sandoz Sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Lanoxin Elx 0.05mg/ml Pediatric; ingredients: Digoxin; parent_key: DB00390.", + "name: Fxt 20; ingredients: Fluoxetine; parent_key: DB00472.", + "name: Apo-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Sertraline-100; ingredients: Sertraline; parent_key: DB01104.", + "name: Lanoxin; ingredients: Digoxin; parent_key: DB00390.", + "name: Mar-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Sertraline Hydrochloride Tablets; ingredients: Sertraline; parent_key: DB01104.", + "name: Venelex; ingredients: Balsam of Peru + Castor oil; parent_key: DB11482.", + "name: Act Sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Flucelvax Quadrivalent (multi-dose Vial); ingredients: Influenza A virus A/Idaho/07/2018 (H1N1) antigen (MDCK cell derived, propiolactone inactivated + Influenza A virus A/Indiana/08/2018 (H3N2) antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Iowa/06/2017 antigen (MDCK cell derived, propiolactone inactivated) + Influenza B virus B/Singapore/INFTT-16-0610/2016 antigen (MDCK cell derived, propiolactone inactivated); parent_key: DB15507.", + "name: Lanoxin Inj 0.05mg/ml Pediatric; ingredients: Digoxin; parent_key: DB00390.", + "name: SERTRALINE HCl; ingredients: Sertraline; parent_key: DB01104.", + "name: SERTRAline Hydrochloride; ingredients: Sertraline; parent_key: DB01104.", + "name: Afluria; ingredients: Influenza A virus A/California/7/2009 X-181 (H1N1) antigen (propiolactone inactivated) + Influenza A virus A/Hong Kong/4801/2014 X-263B (H3N2) antigen (propiolactone inactivated) + Influenza B virus B/Brisbane/60/2008 antigen (propiolactone inactivated); parent_key: DB14459.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14191.", + "name: Sertraline-25; ingredients: Sertraline; parent_key: DB01104.", + "name: PMS-digoxin; ingredients: Digoxin; parent_key: DB00390.", + "name: Lanoxicaps; ingredients: Digoxin; parent_key: DB00390.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB11482.", + "name: Fluvirin; ingredients: Influenza A virus A/California/7/2009 X-181 (H1N1) hemagglutinin antigen (propiolactone inactivated) + Influenza A virus A/Victoria/210/2009 X-187 (H3N2) hemagglutinin antigen (propiolactone inactivated) + Influenza B virus B/Brisbane/60/2008 hemagglutinin antigen (propiolactone inactivated); parent_key: DB11041.", + "name: Jamp-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Ran-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Dom-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: PMS-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Lanoxin Tab 0.0625mg; ingredients: Digoxin; parent_key: DB00390.", + "name: Riva-sertraline; ingredients: Sertraline; parent_key: DB01104.", + "name: Sertraline-50; ingredients: Sertraline; parent_key: DB01104.", + "name: Flulaval Quadrivalent 2013/2014; ingredients: Influenza A virus A/California/7/2009 X-179A (H1N1) antigen (UV, formaldehyde inactivated) + Influenza A virus A/Texas/50/2012 X-223A (H3N2) antigen (UV, formaldehyde inactivated) + Influenza B virus B/Brisbane/60/2008 antigen (UV, formaldehyde inactivated) + Influenza B virus B/Massachusetts/2/2012 BX-51B antigen (UV, formaldehyde inactivated); parent_key: DB14605.", + "name: Apo-digoxin; ingredients: Digoxin; parent_key: DB00390.", + "name: Digitek; ingredients: Digoxin; parent_key: DB00390.", + "name: Fluzone Quadrivalent Southern Hemisphere; ingredients: Influenza A virus A/California/7/2009 X-179A (H1N1) antigen (formaldehyde inactivated) + Influenza A virus A/Hong Kong/4801/2014 X-263B (H3N2) antigen (formaldehyde inactivated) + Influenza B virus B/Brisbane/60/2008 antigen (formaldehyde inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (formaldehyde inactivated); parent_key: DB14457.", + "name: Digoxin; ingredients: Digoxin; parent_key: DB00390.", + "name: Toloxin; ingredients: Digoxin; parent_key: DB00390.", + "name: Zoloft; ingredients: Sertraline; parent_key: DB01104." + ] + }, + { + "example_idx": 103, + "anchor_id": 8413656496129566644, + "positive_id": 18222607152118067265, + "join_paths": [ + [ + 2, + 38, + 0.263671875 + ], + [ + 1, + 38, + 0.2421875 + ], + [ + 2, + 37, + 0.1806640625 + ], + [ + 1, + 37, + 0.162109375 + ] + ], + "rows": [ + "The relative binding affinities (RBA) of two locally used glucocorticoids, rimexolone and flunisolide have been measured for the glucocorticoid receptor of human synovial tissue.", + "The non-fluorinated derivative rimexolone exhibited a binding affinity (RBA of 130) somewhat higher than that of dexamethasone (RBA of 100) but lower than that of flunisolide (RBA 190).", + "Potential metabolites of rimexolone hydroxolated at the C17 side-chain, showed decreased binding affinities, while the 6-hydroxy metabolite of rimexolone and flunisolide (its main metabolite) and the 4,5-dihydro metabolites of rimexolone hardly bound at all.", + "These results support previous pharmacological findings that the high ratio of local to systemic effects of both compounds are due to a pronounced receptor affinity of the parent compounds and the fast systemic metabolism to derivatives with low pharmacodynamic activity.", + "Anti-Inflammatory Agents\nCytosol\nFluocinolone Acetonide\nHumans\nIn Vitro Techniques\nMolecular Structure\nPregnadienes\nReceptors, Glucocorticoid\nSynovial Membrane" + ], + "sentences": [ + "name: Nasarel; ingredients: Flunisolide; parent_key: DB00180.", + "name: Dexamethasone Sodium Phosphate 0.1% / Finasteride 0.1% / Minoxidil 5%; ingredients: Dexamethasone + Finasteride + Minoxidil; parent_key: DB01234.", + "name: Derma-Smoothe/FS; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Xilapak; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Encor Dec Model 033-448 Imp 0.5mg/imp; ingredients: Dexamethasone; parent_key: DB01234.", + "name: Fluocinolone Acetonide Oil; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Proderm; ingredients: Balsam of Peru + Castor oil; parent_key: DB11482.", + "name: Synalar Ont Regular 0.025%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Aerospan; ingredients: Flunisolide; parent_key: DB00180.", + "name: Fluocinolone Acetonide; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Synamol Regular 0.025% Cream; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Ratio-flunisolide; ingredients: Flunisolide; parent_key: DB00180.", + "name: Retisert; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Novolin N; ingredients: Insulin human; parent_key: DB00030.", + "name: Derma Smoothe/fs Liq 0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: FS Shampoo-0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: DermOtic; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Synalar TS; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Synalar Solution 0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Fluocinolone acetonide 0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Flac Otic Oil; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Dermotic Oil Ear Drops; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Synalar Ointment; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Insulatard Flexpen; ingredients: Insulin human; parent_key: DB00030.", + "name: Yutiq; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Immune Globulin Intravenous (human) 5%; ingredients: Human immunoglobulin G; parent_key: DB00028.", + "name: Fluoderm Crm 0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Fluocinolone acetonide; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Fluoderm Ont 0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Keloid Healer Synergy for treatment of keloids; ingredients: Balsam of Peru + Eucalyptol; parent_key: DB03852.", + "name: Capex; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Synalar Cream Mild 0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Flunisolide; ingredients: Flunisolide; parent_key: DB00180.", + "name: Iluvien; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: PMS-flunisolide; ingredients: Flunisolide; parent_key: DB00180.", + "name: Fluocinolone Acetonide Topical; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Beriplex P/n 500; ingredients: Coagulation Factor IX Human + Coagulation factor VII human + Coagulation factor X human + Protein C + Protein S human + Prothrombin; parent_key: DB13152.", + "name: Vexol Ophthalmic Suspension - 1%; ingredients: Rimexolone; parent_key: DB00896.", + "name: Vexol; ingredients: Rimexolone; parent_key: DB00896.", + "name: Fluocinolone Acetonide Topical Solution USP, 0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Fluoderm Crm 0.025%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Aerobid; ingredients: Flunisolide; parent_key: DB00180.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14201.", + "name: Synamol Mild 0.01% Cream; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Aerobid-M; ingredients: Flunisolide; parent_key: DB00180.", + "name: Synalar Ointment Mild 0.01%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Synalar Cream 0.025%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB00994.", + "name: Fluoderm Ont 0.025%; ingredients: Fluocinolone acetonide; parent_key: DB00591.", + "name: Synalar; ingredients: Fluocinolone acetonide; parent_key: DB00591." + ] + }, + { + "example_idx": 104, + "anchor_id": 12040516816466311305, + "positive_id": 9749380989734000411, + "join_paths": [ + [ + 0, + 23, + 0.326171875 + ], + [ + 0, + 37, + 0.326171875 + ], + [ + 0, + 44, + 0.310546875 + ], + [ + 0, + 6, + 0.302734375 + ], + [ + 0, + 1, + 0.2890625 + ] + ], + "rows": [ + "Memantine (MEM) is prescribed in mono and combination therapies for treating the symptoms of moderate to severe Alzheimer's disease (AD).", + "Despite MEM being widely prescribed with other AD and non-AD medicines, very little is known about its mechanism of transport across the blood-brain barrier (BBB), and whether the nature of this transport lends MEM to a potential for drug-drug interactions at the BBB.", + "Therefore, the purpose of this study was to characterize the mechanisms facilitating MEM brain uptake in Swiss Outbred mice using an in situ transcardiac perfusion technique, and identify the putative transporter involved in MEM disposition into the brain.", + "Following transcardiac perfusion of MEM with increasing concentrations, the brain uptake of MEM was observed to be saturable.", + "Furthermore, MEM brain uptake was reduced (up to 55%) by various cationic transporter inhibitors (amantadine, quinine, tetraethylammonium, choline and carnitine) and was dependent on extracellular pH, while being independent of membrane depolarization and the presence of Na(+) in the perfusate.", + "In addition, MEM brain uptake was observed to be sensitive to changes in intracellular pH, hence, likely to be driven by H(+)/MEM antiport mechanisms.", + "Taken together, these findings implicate the involvement of an organic cation transporter regulated by proton antiport mechanisms in the transport of MEM across the mouse BBB, possibly the organic cation/carnitine transporter, OCTN1.", + "These studies also clearly demonstrate the brain uptake of MEM is significantly reduced by other cationic compounds, highlighting the need to consider the possibility of drug interactions with MEM at the BBB, potentially leading to reduced brain uptake and, therefore, altered efficacy of MEM when used in patients on multidrug regimens.", + "Animals\nAntiporters\nBiological Transport\nBlood-Brain Barrier\nCarrier Proteins\nCations\nHydrogen\nHydrogen-Ion Concentration\nMale\nMemantine\nMembrane Proteins\nMembrane Transport Proteins\nMice\nOrganic Cation Transport Proteins\nSymporters" + ], + "sentences": [ + "name: Amantadine hydrochloride; ingredients: Amantadine; parent_key: DB00915.", + "name: Memantine hydrochloride; ingredients: Memantine; parent_key: DB01043.", + "name: Teva-quinine; ingredients: Quinine; parent_key: DB00468.", + "name: SALON CODE Glam Hair Color Glam Cacao; ingredients: Hydrogen peroxide + p-Aminophenol; parent_key: DB14144.", + "name: Pdp-amantadine Hydrochloride Syrup; ingredients: Amantadine; parent_key: DB00915.", + "name: Antibacterial hand washing gel; ingredients: Ethanol + Silver cation; parent_key: DB00898.", + "name: Memantine Accord; ingredients: Memantine; parent_key: DB01043.", + "name: Mylan-amantadine; ingredients: Amantadine; parent_key: DB00915.", + "name: Quinine Sulfate Cap 300mg; ingredients: Quinine; parent_key: DB00468.", + "name: Ratio-memantine; ingredients: Memantine; parent_key: DB01043.", + "name: Vita-worth B-complex Tablets; ingredients: Biotin + Choline + Cyanocobalamin + Folic acid + Inositol + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine; parent_key: DB00152.", + "name: Perineze Triple Dye; ingredients: Brilliant green cation + Gentian violet cation + Proflavine; parent_key: DB01123.", + "name: Magnum-75 Vitamin and Mineral Supplement; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Biotin + Choline + Chromium + Cyanocobalamin + Ergocalciferol + Ferrous gluconate + Folic acid + Inositol + Iodine + Manganese + Nicotinamide + Pantothenic acid + Potassium + Pyridoxine + Riboflavin + Selenium + Thiamine + Vitamin A + Zinc; parent_key: DB00153.", + "name: Vitaplex; ingredients: Ascorbic acid + Biotin + Calcium + Choline + Copper + Cyanocobalamin + Ferrous fumarate + Folic acid + Inositol + Magnesium + Nicotinamide + Pantothenic acid + Potassium Iodide + Pyridoxine + Riboflavin + Thiamine + Vitamin A + Vitamin D + Vitamin E; parent_key: DB00152.", + "name: Osmolex ER; ingredients: Amantadine + Amantadine; parent_key: DB00915.", + "name: Osmolex ER; ingredients: Amantadine; parent_key: DB00915.", + "name: Memantine Hydrochloride; ingredients: Memantine; parent_key: DB01043.", + "name: Ancos Silver Ion Hand Sanitizer; ingredients: Ethanol + Silver cation; parent_key: DB00898.", + "name: Symmetrel; ingredients: Amantadine; parent_key: DB00915.", + "name: Riva-memantine; ingredients: Memantine; parent_key: DB01043.", + "name: Dom-amantadine Hydrochloride Capsules-100mg; ingredients: Amantadine; parent_key: DB00915.", + "name: Hydrogen Peroxide Topical Sol USP 3%; ingredients: Hydrogen peroxide; parent_key: DB11091.", + "name: Memantine Merz; ingredients: Memantine; parent_key: DB01043.", + "name: Memantine Ratiopharm; ingredients: Memantine; parent_key: DB01043.", + "name: Namenda XR; ingredients: Memantine + Memantine + Memantine + Memantine; parent_key: DB01043.", + "name: Endantadine Cap 100mg; ingredients: Amantadine; parent_key: DB00915.", + "name: Quinine - Odan; ingredients: Quinine; parent_key: DB00468.", + "name: Endantadine; ingredients: Amantadine; parent_key: DB00915.", + "name: Innoprax-5; ingredients: Amantadine + Baclofen + Diclofenac + Gabapentin + Lidocaine; parent_key: DB00915.", + "name: Orajel 3X Medicated For Toothache and Gum; ingredients: Benzocaine + Levomenthol + Zinc cation; parent_key: DB01086.", + "name: NinePercent; ingredients: Sodium cation; parent_key: DB14516.", + "name: Only One - Tablet; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Choline + Chromium + Copper + Cyanocobalamin + D-alpha-Tocopherol acetate + Ferrous fumarate + Folic acid + Inositol + Magnesium + Manganese + Molybdenum + Niacin + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Racemethionine + Riboflavin + Selenium + Thiamine + Vanadium + Vitamin A + Zinc; parent_key: DB01373.", + "name: Quinine Sulfate Capsules 300mg; ingredients: Quinine; parent_key: DB00468.", + "name: Vita B Complex Tab; ingredients: Biotin + Choline + Cyanocobalamin + Folic acid + Inositol + Niacin + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine; parent_key: DB00121.", + "name: Lovefun and Duozi Anti-Bacterial Instant hand sanitizer; ingredients: Ethanol + Silver cation; parent_key: DB14521.", + "name: Namenda XR; ingredients: Memantine; parent_key: DB01043.", + "name: PHL-amantadine; ingredients: Amantadine; parent_key: DB00915.", + "name: Memantine; ingredients: Memantine; parent_key: DB01043.", + "name: Antibacterial hand washing gel; ingredients: Ethanol + Silver cation; parent_key: DB14521.", + "name: Ultra Hr; ingredients: Ascorbic acid + Beta carotene + Biotin + Choline + Folic acid + Inositol + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Zinc; parent_key: DB00121.", + "name: Qualaquin; ingredients: Quinine; parent_key: DB00468.", + "name: Pro-quinine - 200; ingredients: Quinine; parent_key: DB00468.", + "name: Kerr 100 Triple Dye Dispos-A; ingredients: Brilliant green cation + Gentian violet cation + Proflavine; parent_key: DB00406.", + "name: Quinine Sulfate Cap 200mg; ingredients: Quinine; parent_key: DB00468.", + "name: Sandoz Memantine; ingredients: Memantine; parent_key: DB01043.", + "name: PHL-amantadine Syrup 10mg/ml; ingredients: Amantadine; parent_key: DB00915.", + "name: Trilisate Tab; ingredients: Choline salicylate + Magnesium salicylate; parent_key: DB14006.", + "name: Namenda; ingredients: Memantine; parent_key: DB01043.", + "name: Symmetrel Capsules 100mg; ingredients: Amantadine; parent_key: DB00915.", + "name: Kerr 100 Triple Dye Dispos-A; ingredients: Brilliant green cation + Gentian violet cation + Proflavine; parent_key: DB11279." + ] + }, + { + "example_idx": 105, + "anchor_id": 9774895948882677967, + "positive_id": 12384092252514622939, + "join_paths": [ + [ + 3, + 22, + 0.208984375 + ], + [ + 3, + 23, + 0.20703125 + ], + [ + 3, + 26, + 0.205078125 + ], + [ + 3, + 13, + 0.2041015625 + ], + [ + 3, + 16, + 0.2041015625 + ] + ], + "rows": [ + "Concatenation of engineered biocatalysts into multistep pathways markedly increases their utility, but the development of generalizable assembly methods remains a major challenge.", + "Herein we evaluate 'bioretrosynthesis', which is an application of the retrograde evolution hypothesis, for biosynthetic pathway construction.", + "To test bioretrosynthesis, we engineered a pathway for synthesis of the antiretroviral nucleoside analog didanosine (2',3'-dideoxyinosine).", + "Applying both directed evolution- and structure-based approaches, we began pathway construction with a retro-extension from an engineered purine nucleoside phosphorylase and evolved 1,5-phosphopentomutase to accept the substrate 2,3-dideoxyribose 5-phosphate with a 700-fold change in substrate selectivity and threefold increased turnover in cell lysate.", + "A subsequent retrograde pathway extension, via ribokinase engineering, resulted in a didanosine pathway with a 9,500-fold change in nucleoside production selectivity and 50-fold increase in didanosine production.", + "Unexpectedly, the result of this bioretrosynthetic step was not a retro-extension from phosphopentomutase but rather the discovery of a fortuitous pathway-shortening bypass via the engineered ribokinase.", + "Biocatalysis\nDidanosine\nDirected Molecular Evolution\nEnzymes\nModels, Molecular" + ], + "sentences": [ + "id: BE0000882; name: Trifunctional purine biosynthetic protein adenosine-3; organism: Humans; known_action: unknown; parent_key: DB02236.", + "id: BE0001576; name: Purine nucleoside phosphorylase; organism: Mycobacterium tuberculosis; known_action: unknown; parent_key: DB03551.", + "id: BE0002011; name: Purine nucleoside phosphorylase DeoD-type; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02113.", + "id: BE0001556; name: Purine nucleoside phosphorylase 2; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02377.", + "id: BE0004382; name: Mediator of RNA polymerase II transcription subunit 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB04891.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB04076.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB02377.", + "id: BE0009195; name: High molecular weight rhoptry protein 2; organism: Plasmodium falciparum (isolate 3D7); known_action: unknown; position: 113; parent_key: DB11638.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB02568.", + "id: BE0000977; name: Insulin receptor substrate 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB08513.", + "id: BE0001380; name: Cell division protein FtsZ; organism: Mycobacterium tuberculosis; known_action: unknown; parent_key: DB04315.", + "id: BE0001997; name: Ribokinase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB01936.", + "id: BE0001997; name: Ribokinase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03909.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB02230.", + "id: BE0009788; name: Phosphodiesterase enzymes; organism: Humans; known_action: yes; position: 5; parent_key: DB00806.", + "id: BE0000882; name: Trifunctional purine biosynthetic protein adenosine-3; organism: Humans; known_action: unknown; parent_key: DB03546.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB03609.", + "id: BE0003786; name: Low molecular weight phosphotyrosine protein phosphatase; organism: Humans; known_action: unknown; position: 1; parent_key: DB04214.", + "id: BE0001623; name: Purine nucleoside phosphorylase; organism: Cellulomonas sp.; known_action: unknown; parent_key: DB02985.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB01667.", + "id: BE0000967; name: Tissue factor pathway inhibitor; organism: Humans; known_action: yes; position: 1; parent_key: DB14562.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB02391.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; position: 2; parent_key: DB00900.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB03101.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: yes; position: 10; parent_key: DB00242.", + "id: BE0000882; name: Trifunctional purine biosynthetic protein adenosine-3; organism: Humans; known_action: yes; position: 4; parent_key: DB00642.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB03881.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB02222.", + "id: BE0002734; name: Purine nucleoside phosphorylase; organism: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099); known_action: unknown; parent_key: DB02377.", + "id: BE0009789; name: Phosphodiesterase enzymes; organism: Humans; known_action: yes; position: 23; parent_key: DB00201.", + "id: BE0001997; name: Ribokinase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04444.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB02857.", + "id: BE0001423; name: Glutamine--fructose-6-phosphate aminotransferase [isomerizing]; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02445.", + "id: BE0000967; name: Tissue factor pathway inhibitor; organism: Humans; known_action: yes; position: 3; parent_key: DB06779.", + "id: BE0001576; name: Purine nucleoside phosphorylase; organism: Mycobacterium tuberculosis; known_action: unknown; parent_key: DB03411.", + "id: BE0003786; name: Low molecular weight phosphotyrosine protein phosphatase; organism: Humans; known_action: unknown; parent_key: DB00173.", + "id: BE0002011; name: Purine nucleoside phosphorylase DeoD-type; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02934.", + "id: BE0001556; name: Purine nucleoside phosphorylase 2; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02134.", + "id: BE0001626; name: Glucosamine-6-phosphate deaminase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03951.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB03551.", + "id: BE0000967; name: Tissue factor pathway inhibitor; organism: Humans; known_action: unknown; parent_key: DB00036.", + "id: BE0002841; name: Purine nucleoside phosphorylase; organism: Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579); known_action: unknown; parent_key: DB02857.", + "id: BE0009711; name: Bacterial beta-lactamase enzymes; known_action: unknown; position: 2; parent_key: DB00766.", + "id: BE0001749; name: High-molecular-weight cytochrome c; organism: Desulfovibrio vulgaris (strain Hildenborough / ATCC 29579 / NCIMB 8303); known_action: unknown; parent_key: DB03317.", + "id: BE0003774; name: BAG family molecular chaperone regulator 1; organism: Humans; known_action: unknown; position: 1; parent_key: DB07045.", + "id: BE0000674; name: Myeloid cell surface antigen CD33; organism: Humans; known_action: yes; parent_key: DB00056.", + "id: BE0003436; name: Programmed cell death protein 1; organism: Humans; known_action: yes; position: 1; parent_key: DB09037.", + "id: BE0003106; name: Nucleoside diphosphate kinase A; organism: Humans; known_action: unknown; position: 30; parent_key: DB09130.", + "id: BE0002011; name: Purine nucleoside phosphorylase DeoD-type; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04198.", + "id: BE0000250; name: Purine nucleoside phosphorylase; organism: Humans; known_action: unknown; parent_key: DB02796." + ] + }, + { + "example_idx": 106, + "anchor_id": 788973434249662393, + "positive_id": 5065341772665897474, + "join_paths": [ + [ + 6, + 32, + 0.3828125 + ], + [ + 6, + 40, + 0.33984375 + ], + [ + 12, + 42, + 0.3359375 + ], + [ + 12, + 8, + 0.330078125 + ], + [ + 12, + 49, + 0.330078125 + ] + ], + "rows": [ + "In a therapeutic trial, the effect of short-term low-dosage N-acetylcysteine supplementation on glutathione metabolism was investigated in two patients with hereditary glutathione deficiency (5-oxoprolinuria).", + "Clinical and neurophysiological examinations of the patients indicated progressive neurological damage.", + "The pretreatment concentrations of total and free glutathione in leukocytes were 15-20% of normal, whereas the corresponding gamma-glutamylcysteine levels were increased.", + "In plasma, the glutathione concentrations were similarly decreased, but no gamma-glutamylcysteine was detected.", + "Total glutathione in erythrocytes was markedly decreased.", + "Low urinary excretion of cysteinylglycine, cyst(e)ine, taurine, N-acetylcysteine, mercaptolactate and mercaptoacetate and reduced leukocyte taurine levels constituted additional evidence of decreased intracellular availability of cysteine, i.e.", + "glutathione.", + "Oral supplementation with N-acetylcysteine (5 mg/kg x 3/day) had no effect on acid-base balance, erythrocyte glutathione levels or 5-oxoproline concentrations in plasma and urine.", + "In leukocytes, the glutathione concentrations were increased by 20-30%, whereas the gamma-glutamylcysteine levels were essentially unaltered.", + "In parallel, the urinary excretion of cysteinylglycine was increased and the leukocyte levels and urinary outputs of sulphur amino acids were restored.", + "No side-effects of the treatment were noted.", + "The results indicate that N-acetylcysteine may be of value in increasing the low intracellular glutathione concentrations and cysteine availability in patients with hereditary glutathione synthetase deficiency.", + "Acetylcysteine\nAdolescent\nAmino Acids, Sulfur\nFemale\nGlutathione\nGlutathione Synthase\nHumans\nLeukocytes\nPeptide Synthases\nPyrrolidonecarboxylic Acid" + ], + "sentences": [ + "id: BE0000185; name: Glutathione synthetase; organism: Humans; known_action: unknown; parent_key: DB04395.", + "id: BE0000185; name: Glutathione synthetase; organism: Humans; known_action: yes; position: 1; parent_key: DB06151.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB02633.", + "id: BE0000763; name: Methionine synthase reductase; organism: Humans; known_action: unknown; position: 3; parent_key: DB00115.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB04132.", + "id: BE0000375; name: Sodium- and chloride-dependent creatine transporter 1; organism: Humans; known_action: yes; position: 2; parent_key: DB13191.", + "id: BE0001271; name: ATP-dependent dethiobiotin synthetase BioD 1; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03775.", + "id: BE0001777; name: Bile acid receptor; organism: Humans; known_action: unknown; position: 2; parent_key: DB04348.", + "id: BE0000185; name: Glutathione synthetase; organism: Humans; known_action: unknown; parent_key: DB00143.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 10; parent_key: DB03619.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB03814.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 1; parent_key: DB06246.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB00143.", + "id: BE0002659; name: Glutathione S-transferase; organism: Plasmodium falciparum; known_action: unknown; position: 5; parent_key: DB00608.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB05460.", + "id: BE0000298; name: Glutathione reductase; organism: Escherichia coli (strain K12); known_action: yes; parent_key: DB00336.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 1; parent_key: DB08370.", + "id: BE0009326; name: 30 kDa immediate-early protein 2; organism: Human cytomegalovirus (strain Towne); known_action: yes; position: 1; parent_key: DB06759.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB03686.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 12; parent_key: DB14635.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 3; parent_key: DB13014.", + "id: BE0004124; name: Glutathione S-transferase; organism: Burkholderia xenovorans (strain LB400); known_action: unknown; position: 1; parent_key: DB07914.", + "id: BE0002981; name: Glutathione reductase; organism: Plasmodium falciparum (isolate K1 / Thailand); known_action: unknown; parent_key: DB03147.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 22; parent_key: DB00197.", + "id: BE0000185; name: Glutathione synthetase; organism: Humans; known_action: unknown; position: 8; parent_key: DB00145.", + "id: BE0002286; name: Glutathione peroxidase 6; organism: Humans; known_action: unknown; parent_key: DB00143.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 5; parent_key: DB11672.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB04972.", + "id: BE0001035; name: Protein-glutamine gamma-glutamyltransferase 2; organism: Humans; known_action: unknown; parent_key: DB04315.", + "id: BE0002444; name: Squalene synthase; organism: Humans; known_action: unknown; parent_key: DB05317.", + "id: BE0004343; name: Actinorhodin polyketide synthase acyl carrier protein; organism: Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145); known_action: unknown; position: 1; parent_key: DB08585.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 6; parent_key: DB01242.", + "id: BE0005577; name: Glutathione; organism: Humans; known_action: unknown; position: 1; parent_key: DB13145.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 4; parent_key: DB00903.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB03003.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 2; parent_key: DB11831.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB04339.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; parent_key: DB01834.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 1; parent_key: DB07849.", + "id: BE0000814; name: Glutathione S-transferase P; organism: Humans; known_action: unknown; position: 26; parent_key: DB00363.", + "id: BE0009997; name: Glutathione peroxidase; known_action: unknown; position: 9; parent_key: DB00143.", + "id: BE0000185; name: Glutathione synthetase; organism: Humans; known_action: unknown; position: 9; parent_key: DB00151.", + "id: BE0000185; name: Glutathione synthetase; organism: Humans; known_action: unknown; position: 85; parent_key: DB09130.", + "id: BE0001271; name: ATP-dependent dethiobiotin synthetase BioD 1; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB02941.", + "id: BE0000816; name: Glutathione peroxidase 1; organism: Humans; known_action: unknown; position: 47; parent_key: DB09061.", + "id: BE0002659; name: Glutathione S-transferase; organism: Plasmodium falciparum; known_action: unknown; parent_key: DB01942.", + "id: BE0004343; name: Actinorhodin polyketide synthase acyl carrier protein; organism: Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145); known_action: unknown; position: 1; parent_key: DB08586.", + "id: BE0000298; name: Glutathione reductase; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB03147.", + "id: BE0002659; name: Glutathione S-transferase; organism: Plasmodium falciparum; known_action: unknown; parent_key: DB04132.", + "id: BE0000185; name: Glutathione synthetase; organism: Humans; known_action: unknown; parent_key: DB03408." + ] + }, + { + "example_idx": 107, + "anchor_id": 14211446472125932504, + "positive_id": 4390922239705872641, + "join_paths": [ + [ + 5, + 28, + 0.150390625 + ] + ], + "rows": [ + "Mitotane is currently employed as adjuvant therapy as well as in the medical treatment of adrenocortical carcinoma (ACC), alone or in combination with chemotherapeutic agents.", + "It was previously demonstrated that mitotane potentiates chemotherapeutic drugs cytotoxicity in cancer cells displaying chemoresistance due to P-glycoprotein (P-gp), an efflux pump involved in cancer multidrug resistance.", + "The majority of ACC expresses high levels of P-gp and is highly chemoresistent.", + "The aim of our study was to explore in vitro whether mitotane, at concentrations lower than those currently reached in vivo, may sensitize ACC cells to the cytotoxic effects of doxorubicin and whether this effect is due to a direct action on P-gp.", + "NCI-H295 and SW13 cell lines as well as 4 adrenocortical neoplasia primary cultures were treated with mitotane and doxorubicin, and cell viability was measured by MTT assay.", + "P-gp activity was measured by calcein and P-gp-Glo assays.", + "P-gp expression was evaluated by Western blot.", + "We found that very low mitotane concentrations sensitize ACC cells to the cytotoxic effects of doxorubicin, depending on P-gp expression.", + "In addition, mitotane directly inhibits P-gp detoxifying function, allowing doxorubicin cytotoxic activity.", + "These data provide the basis for the greater efficacy of combination therapy (mitotane plus chemotherapeutic drugs) on ACC patients.", + "Shedding light on mitotane mechanisms of action could result in an improved design of drug therapy for patients with ACC.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAdrenal Cortex Neoplasms\nAdrenocortical Carcinoma\nAntibiotics, Antineoplastic\nAntineoplastic Agents, Hormonal\nCell Death\nCell Line, Tumor\nCell Survival\nDoxorubicin\nDrug Interactions\nDrug Therapy, Combination\nHumans\nMitotane" + ], + "sentences": [ + "ref-id: L9827; 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parent_key: DB14500.", + "ref-id: L139; title: Antimicrobial agents and Chemotherapy; url: http://aac.asm.org/cgi/content/full/44/7/1925; parent_key: DB06696.", + "ref-id: L2000; title: Vinorelbine, Ontario Cancer Care; url: https://www.cancercareontario.ca/en/system/.../vinorelbine.pdf; parent_key: DB00361.", + "ref-id: L12249; title: FDA Approved Drug Products: Increlex Mecasermin Subcutaneous Injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021839s024lbl.pdf; parent_key: DB01277.", + "ref-id: L1931; title: National Cancer Institute; url: https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq; parent_key: DB09053.", + "ref-id: L10403; title: FDA approves Global Blood Therapeutics sickle cell disease drug; url: https://www.reuters.com/article/us-global-blood-theraprutics-fda/fda-approves-global-blood-therapeutics-sickle-cell-disease-drug-idUSKBN1XZ2E5; parent_key: DB14975.", + "ref-id: L1651; title: Cancer; url: https://www.cancer.org/cancer/small-cell-lung-cancer/about/what-is-small-cell-lung-cancer.html; parent_key: DB09336.", + "ref-id: L12567; title: FDA Approved Drug Products: Livalo (pitavastatin) oral tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022363s017lbl.pdf; parent_key: DB08860.", + "ref-id: L803; title: Rhophylac Summary of Basis for Approval; url: https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM119475.pdf; parent_key: DB11597.", + "ref-id: L2234; title: Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336293/; parent_key: DB13257.", + "ref-id: L12153; title: NIH StatPearls: Cholesterol levels; url: https://www.ncbi.nlm.nih.gov/books/NBK542294/; parent_key: DB11936.", + "ref-id: L13808; title: FDA Approved Drug Products: Boniva Ibandronate Intravenous Injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021858s022lbl.pdf; parent_key: DB00710.", + "ref-id: L2096; title: Zinc Transporters, Mechanisms of Action and Therapeutic Utility: Implications for Type 2 Diabetes Mellitus; url: https://www.hindawi.com/journals/jnme/2012/173712/; parent_key: DB01593.", + "ref-id: L1504; title: Vaya Direct; url: https://vayadirect.com; parent_key: DB09328.", + "ref-id: L13874; title: NIH: Clinical Trial to Evaluate the Efficacy and Safety of an Immunomodulatory Therapy for the Treatment of Patients With Moderate to Severe COVID-19 Infection (NCT04374032); url: https://clinicaltrials.gov/ct2/show/NCT04374032; parent_key: DB15687.", + "ref-id: L2113; title: Gelatin Supplements, Medline plus; url: https://medlineplus.gov/druginfo/natural/1051.html; parent_key: DB11242.", + "ref-id: L2373; title: NIH National Cancer Institute Dictionary of Cancer Terms: Anetholtrithione; url: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/anetholtrithione; parent_key: DB13853.", + "ref-id: L2097; title: Zinc, future mono/adjunctive therapy for depression: Mechanisms of antidepressant action; url: https://www.sciencedirect.com/science/article/abs/pii/S1734114015000274; parent_key: DB01593.", + "ref-id: L1468; title: Anti-tumor effects of bemiparin in HepG2 and MIA PaCa-2 cells; url: https://pdfs.semanticscholar.org/e190/2ca30f2548cfa7f02e2b815705137ace90e3.pdf; parent_key: DB09258.", + "ref-id: L2096; title: Zinc Transporters, Mechanisms of Action and Therapeutic Utility: Implications for Type 2 Diabetes Mellitus; url: https://www.hindawi.com/journals/jnme/2012/173712/; parent_key: DB14487.", + "ref-id: L3341; title: Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression; url: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2199-z; parent_key: DB11967.", + "ref-id: L1643; title: Bioactivity of synthetic human cholecystokinin (CCK)-33 in vitro and in vivo; url: https://link.springer.com/article/10.1007%2FBF02779509; parent_key: DB08862.", + "ref-id: L13874; title: NIH: Clinical Trial to Evaluate the Efficacy and Safety of an Immunomodulatory Therapy for the Treatment of Patients With Moderate to Severe COVID-19 Infection (NCT04374032); url: https://clinicaltrials.gov/ct2/show/NCT04374032; parent_key: DB12668.", + "ref-id: L5503; title: American Society of Hematology Blood: Efficacy of an Extended Half-Life GlycoPEGylated rFVIII (N8-GP): Pooled Analysis of ABR (Results from Two Clinical Trials); url: http://www.bloodjournal.org/content/132/Suppl_1/1177?sso-checked=true&utm_source=TrendMD&utm_medium=cpc&utm_campaign=Blood_TrendMD_0; parent_key: DB14738.", + "ref-id: L7102; title: Nitroglycerin pump spray monograph; url: http://products.sanofi.ca/en/nitrolingual-pumpspray.pdf; parent_key: DB00727.", + "ref-id: L1557; title: National Cancer Institute; url: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/tegafur-uracil; parent_key: DB09327.", + "ref-id: L2226; title: Meeting the vitamin A requirements; url: https://www.hindawi.com/journals/tswj/2016/7393620/; parent_key: DB06755.", + "ref-id: L13035; title: FDA Approved Products: DRAXIMAGE® MDP-25 (Kit for the Preparation of Technetium Tc 99m Medronate Injection); 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title: FDA Approved Drugs: Azelastine nasal spray; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020114s028lbl.pdf; parent_key: DB00972.", + "ref-id: L2840; title: Tossamin Plus; url: https://www.sdrugs.com/?c=drug&s=tossamin%20plus&ingredient=codeine%20phosphate%20hemihydrate/diphenhydramine%20hydrochloride/methylephedrine%20hydrochloride/noscapine; parent_key: DB11278.", + "ref-id: L2622; title: National Cancer Institute; url: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C61621; parent_key: DB13268.", + "ref-id: L1934; title: American Cancer Society; url: https://www.cancer.org/cancer/waldenstrom-macroglobulinemia/about/what-is-wm.html; parent_key: DB09053.", + "ref-id: L2384; title: Vitamin E Regulatory Mechanisms; url: https://www.annualreviews.org/doi/abs/10.1146/annurev.nutr.27.061406.093819; parent_key: DB11635.", + "ref-id: L1308; title: NCI dictionary; url: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/polaprezinc; parent_key: DB09221.", + "ref-id: L2087; title: Zinc Medline Plus; url: https://medlineplus.gov/druginfo/natural/982.html; parent_key: DB11248.", + "ref-id: L291; title: Iodophore activity, CDC; url: https://www.cdc.gov/hicpac/Disinfection_Sterilization/8_0Iodophors.html; parent_key: DB06812.", + "ref-id: L2407; title: National Cancer Institute; url: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C87662; parent_key: DB13421.", + "ref-id: L2543; title: VIVO pathophysiology; url: http://www.vivo.colostate.edu/hbooks/pathphys/digestion/pancreas/exocrine.html; parent_key: DB11066.", + "ref-id: L342; title: FDA data; url: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/Darvocet-N_July2009.pdf; parent_key: DB00647.", + "ref-id: L356; title: Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771396/; parent_key: DB11737.", + "ref-id: L11007; title: FDA Approved Drug Products: Hydroxyzine HCl oral tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/088617Orig1s043,088618Orig1s043,088619Orig1s044lbl.pdf; parent_key: DB00557.", + "ref-id: L3739; title: FDA Approves Radiation Medical Countermeasure; url: https://www.fda.gov/emergencypreparedness/counterterrorism/medicalcountermeasures/aboutmcmi/ucm443245.htm; parent_key: DB00099." + ] + }, + { + "example_idx": 108, + "anchor_id": 5733674769209884872, + "positive_id": 15637226764861254714, + "join_paths": [ + [ + 1, + 6, + 0.26171875 + ], + [ + 4, + 6, + 0.251953125 + ], + [ + 1, + 18, + 0.25 + ], + [ + 1, + 47, + 0.2490234375 + ], + [ + 4, + 18, + 0.2490234375 + ] + ], + "rows": [ + "PURPOSE: Previous studies show that inhibition of ABCB1 expression overcomes acquired docetaxel resistance in C4-2B-TaxR cells.", + "In this study, we examined whether antiandrogens, such as bicalutamide and enzalutamide, could inhibit ABCB1 activity and overcome resistance to docetaxel.", + "EXPERIMENTAL DESIGN: ABCB1 efflux activity was determined using a rhodamine efflux assay.", + "ABCB1 ATPase activity was determined by Pgp-Glo assay systems.", + "The effects of the antiandrogens bicalutamide and enzalutamide on docetaxel sensitivity were determined by cell growth assays and tumor growth in vivo.", + "RESULTS: We found that bicalutamide and enzalutamide inhibit ABCB1 ATP-binding cassette transporter activity through blocking ABCB1 efflux activity.", + "Bicalutamide inhibited ABCB1 efflux activity by 40%, whereas enzalutamide inhibited ABCB1 efflux activity by approximately 60%.", + "Both bicalutamide and enzalutamide inhibit ABCB1 ATPase activity.", + "In addition, bicalutamide and enzalutamide inhibit ABCB1 efflux activity and desensitize docetaxel-resistant and androgen receptor (AR)-negative DU145 cells.", + "Combination of bicalutamide with docetaxel had a significant antitumor effect in both AR-positive and AR-negative docetaxel-resistant xenograft models, suggesting that bicalutamide desensitizes docetaxel-resistant cells to docetaxel treatment independent of AR status.", + "CONCLUSIONS: We identified a novel mechanism of action for antiandrogens such as bicalutamide and enzalutamide as inhibitors of ABCB1 efflux and ATPase activity.", + "Bicalutamide and enzalutamide desensitize docetaxel-resistant prostate cancer cells to docetaxel treatment independent of AR status.", + "These studies may lead to the development of combinational therapies with bicalutamide/enzalutamide and docetaxel as effective regimens to treat advanced prostate cancer independent of AR status, and possibly other types of cancer.", + "ATP Binding Cassette Transporter, Subfamily B\nAdenosine Triphosphatases\nAdenosine Triphosphate\nAndrogen Antagonists\nAnilides\nAnimals\nAntineoplastic Combined Chemotherapy Protocols\nCell Line, Tumor\nDocetaxel\nDrug Resistance, Neoplasm\nGene Expression Regulation, Neoplastic\nHumans\nMale\nMice\nNitriles\nPhenylthiohydantoin\nProstatic Neoplasms\nProstatic Neoplasms, Castration-Resistant\nReceptors, Androgen\nRhodamines\nTaxoids\nTosyl Compounds\nXenograft Model Antitumor Assays" + ], + "sentences": [ + "name: Ran-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Taxotere; ingredients: Docetaxel; parent_key: DB01248.", + "name: PegIntron; ingredients: Peginterferon alfa-2b; parent_key: DB00022.", + "name: Ava-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Apo-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Docetaxel Accord; ingredients: Docetaxel; parent_key: DB01248.", + "name: Docetaxel; ingredients: Docetaxel; parent_key: DB01248.", + "name: Aprilskin Magic Snow Fixing Foundation 22 Pink Beige; ingredients: Adenosine + Nicotinamide + Titanium dioxide; parent_key: DB09536.", + "name: SuperPlus Beblesh Balm SPF25 PA 2Plus; ingredients: Adenosine + Arbutin + Octinoxate + Octisalate + Titanium dioxide + Zinc oxide; parent_key: DB09536.", + "name: Nu-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Bring Green Carrot Vita Dark Spot Serum; ingredients: Adenosine + Nicotinamide; parent_key: DB02701.", + "name: Bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Dom-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Ag-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Docetaxel Kabi; ingredients: Docetaxel; parent_key: DB01248.", + "name: Volcanic Homme; ingredients: Adenosine + Nicotinamide; parent_key: DB02701.", + "name: Docetaxel Non-Alcohol Formula; ingredients: Docetaxel; parent_key: DB01248.", + "name: Ach-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Docetaxel Injection; ingredients: Docetaxel; parent_key: DB01248.", + "name: Skinfood Royal Honey Essential Eye; ingredients: Adenosine; parent_key: DB00640.", + "name: Docetaxel Injection USP; ingredients: Docetaxel; parent_key: DB01248.", + "name: Docefrez; ingredients: Docetaxel; parent_key: DB01248.", + "name: Teva-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Med-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: PMS-docetaxel; ingredients: Docetaxel; parent_key: DB01248.", + "name: Accel-bicalutamide Tablets USP; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Pro-bicalutamide - 50; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Docetaxel Mylan; ingredients: Docetaxel; parent_key: DB01248.", + "name: PHL-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Sylatron; ingredients: Peginterferon alfa-2b; parent_key: DB00022.", + "name: Docetaxel Anhydrous; ingredients: Docetaxel; parent_key: DB01248.", + "name: Sandoz Bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Casodex; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Jamp-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Xtandi; ingredients: Enzalutamide; parent_key: DB08899.", + "name: Ntp-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Vitabrid C12 SENSITIVE Spot Pow der Serum; ingredients: Adenosine + Nicotinamide; parent_key: DB00640.", + "name: Ratio-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Bicalutamide Tablets; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Docetaxel Winthrop; ingredients: Docetaxel; parent_key: DB01248.", + "name: Act Bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: PMS-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Taro-docetaxel; ingredients: Docetaxel; parent_key: DB01248.", + "name: Medi Hydro DP Vita C Ampoule; ingredients: Adenosine + Nicotinamide; parent_key: DB02701.", + "name: Van-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Mylan-bicalutamide; ingredients: Bicalutamide; parent_key: DB01128.", + "name: Taxespira; ingredients: Docetaxel; parent_key: DB01248.", + "name: Docetaxel Teva Pharma; ingredients: Docetaxel; parent_key: DB01248.", + "name: Ruby Cell 4u; ingredients: Adenosine + Nicotinamide; parent_key: DB02701.", + "name: Act Docetaxel 40 mg/ml; ingredients: Docetaxel; parent_key: DB01248." + ] + }, + { + "example_idx": 109, + "anchor_id": 5186811174370871131, + "positive_id": 6445443005498037223, + "join_paths": [ + [ + 3, + 47, + 0.306640625 + ], + [ + 4, + 47, + 0.298828125 + ], + [ + 4, + 37, + 0.296875 + ], + [ + 3, + 37, + 0.294921875 + ], + [ + 4, + 38, + 0.2890625 + ] + ], + "rows": [ + "OBJECTIVE: Organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1 gene) is a hepatic uptake transporter, and its genetic variability is associated with pharmacokinetics and muscle toxicity risk of simvastatin.", + "We examined the possible effects of variations in the SLCO1B1 gene on the pharmacokinetics of lovastatin in a prospective genotype panel study.", + "PARTICIPANTS AND METHODS: Seven healthy volunteers with the SLCO1B1*1B/*1B genotype, five with the SLCO1B1*5/*15 or *15/*15 genotype, and 15 with the SLCO1B1*1A/*1A genotype (controls) were recruited.", + "Each study participant ingested a single 40-mg dose of lovastatin.", + "Plasma concentrations of lovastatin (inactive lactone) and its active metabolite lovastatin acid were measured up to 24 h.\nRESULTS: In the SLCO1B1*5/*15 or *15/*15 genotype group, the geometric mean Cmax and AUC0-24 of lovastatin acid were 340 and 286% of the corresponding values in the SLCO1B1*1A/*1A (reference) genotype group (P<0.005).", + "In contrast, the AUC0-24 of lovastatin acid in the SLCO1B1*1B/*1B genotype group was only 68% of that in the reference genotype group (P=0.03).", + "No statistically significant association was observed between the SLCO1B1 genotype and the pharmacokinetics of lovastatin lactone.", + "CONCLUSION: SLCO1B1*5/*15 and *15/*15 genotypes markedly increase the exposure to active lovastatin acid, but have no significant effect on lovastatin lactone, similar to their effects on simvastatin and simvastatin acid.", + "Accordingly, it is probable that the risk of muscle toxicity during lovastatin treatment is increased in individuals carrying the SLCO1B1*5 or *15 allele.", + "The SLCO1B1*1B/*1B genotype is associated with reduced lovastatin acid concentrations, consistent with enhanced hepatic uptake.", + "Administration, Oral\nAdult\nDose-Response Relationship, Drug\nFemale\nHumans\nLiver-Specific Organic Anion Transporter 1\nLovastatin\nMale\nOrganic Anion Transporters\nPolymorphism, Single Nucleotide" + ], + "sentences": [ + "name: Mencevax Ac Pws Inj 2500mcg/vial; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Sodium chloride; parent_key: DB09153.", + "name: Prim - Royal P.M.T.; ingredients: Ascorbic acid + Chromium + Cyanocobalamin + Folic acid + Iodine + Manganese + Pyridoxine + Riboflavin + Thiamine + Zinc; parent_key: DB00140.", + "name: PMS-simvastatin; ingredients: Simvastatin; parent_key: DB00641.", + "name: Apo-lovastatin - Tab 40mg; ingredients: Lovastatin; parent_key: DB00227.", + "name: Simvastatin Tablets 10mg; ingredients: Simvastatin; parent_key: DB00641.", + "name: Nu-simvastatin Tablets; ingredients: Simvastatin; parent_key: DB00641.", + "name: Menveo; ingredients: Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine + Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13888.", + "name: Cholib; ingredients: Fenofibrate + Simvastatin; parent_key: DB01039.", + "name: Auro-simvastatin; ingredients: Simvastatin; parent_key: DB00641.", + "name: Rebif; ingredients: Interferon beta-1a + Sodium chloride; parent_key: DB00060.", + "name: PreferaOB; ingredients: alpha-Tocopherol succinate + Biotin + Cholecalciferol + Cupric sulfate + Cyanocobalamin + Folic acid + Heme iron polypeptide + Iron Dextran + Nicotinamide + Pantothenic acid + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Thiamine + Zinc oxide; parent_key: DB09321.", + "name: Menhibrix; ingredients: Haemophilus influenzae type B strain 1482 capsular polysaccharide tetanus toxoid conjugate antigen + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group Y; parent_key: DB10076.", + "name: Menomune-A/c/y/w-135; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13888.", + "name: Ratio-simvastatin; ingredients: Simvastatin; parent_key: DB00641.", + "name: Rebif Rebidose; ingredients: Interferon beta-1a + Interferon beta-1a; parent_key: DB00060.", + "name: Avonex Pen; ingredients: Interferon beta-1a; parent_key: DB00060.", + "name: Menomune - A/c/y/w-135 Combined; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13888.", + "name: C-curity-vitamin C Cap; ingredients: Ascorbic acid; parent_key: DB00126.", + "name: Simvastatin-10; ingredients: Simvastatin; parent_key: DB00641.", + "name: Nimenrix; ingredients: Clostridium tetani toxoid antigen (formaldehyde inactivated) + Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB10583.", + "name: Actimmune; ingredients: Interferon gamma-1b; parent_key: DB00033.", + "name: Meningococcal Polysaccharide Vaccine Groups A & C; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C; parent_key: DB13889.", + "name: Mencevax Ac Pws 500mcg/vial; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Sodium chloride; parent_key: DB09153.", + "name: Vitamin B Tablets; ingredients: Biotin + Choline + Cyanocobalamin + Folic acid + Inositol + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine; parent_key: DB00122.", + "name: Glyco Plus Ect; ingredients: Ascorbic acid + Biotin + Choline + Cyanocobalamin + Fish liver oil + Iron + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Selenium + Thiamine + Zinc; parent_key: DB01593.", + "name: Avonex; ingredients: Interferon beta-1a; parent_key: DB02325.", + "name: Nata Komplete; ingredients: Ascorbic acid + Biotin + Calcium + Cholecalciferol + Choline + Copper + Cyanocobalamin + Folic acid + Iron + Magnesium + Niacin + Pantothenic acid + Pyridoxine + Riboflavin + Selenium + Thiamine + Vitamin A + Vitamin E + Zinc; parent_key: DB00140.", + "name: Mencevax Ac Pws 50mcg/vial; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Sodium chloride; parent_key: DB09153.", + "name: Onccor; ingredients: Ascorbic acid + Beta carotene + Biotin + Choline + Chromium + Cupric oxide + Cyanocobalamin + Ergocalciferol + Folic acid + Inositol + Manganese + Molybdenum + Nicotinamide + Pantothenic acid + Potassium + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Thiamine + Vitamin A + Vitamin E + Zinc; parent_key: DB00126.", + "name: Simvastatin Tablets 80mg; ingredients: Simvastatin; parent_key: DB00641.", + "name: Simcor; ingredients: Niacin + Simvastatin; parent_key: DB00641.", + "name: Apo-lovastatin - Tab 20mg; ingredients: Lovastatin; parent_key: DB00227.", + "name: Pharma-simvastatin; ingredients: Simvastatin; parent_key: DB00641.", + "name: Simvastatin-80; ingredients: Simvastatin; parent_key: DB00641.", + "name: Septa-simvastatin; ingredients: Simvastatin; parent_key: DB00641.", + "name: Menomune-A/c/y/w-135; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13887.", + "name: Menveo; ingredients: Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine + Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13890.", + "name: Lovastatin-20; ingredients: Lovastatin; parent_key: DB00227.", + "name: Ratio-lovastatin; ingredients: Lovastatin; parent_key: DB00227.", + "name: Menveo; ingredients: Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine + Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13889.", + "name: Avonex; ingredients: Interferon beta-1a + Water; parent_key: DB09145.", + "name: Betaferon; ingredients: Interferon beta-1b; parent_key: DB00068.", + "name: Swiss One; ingredients: Ascorbic acid + Biotin + Calcium + Choline + Chromium + Copper + Cyanocobalamin + Ferrous fumarate + Folic acid + Inositol + Iodine + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Potassium + Pyridoxine + Riboflavin + Thiamine + Vitamin A + Vitamin D + Vitamin E + Zinc; parent_key: DB00121.", + "name: Dom-lovastatin; ingredients: Lovastatin; parent_key: DB00227.", + "name: PreferaOB One; ingredients: Ascorbic acid + Biotin + Cholecalciferol + Cyanocobalamin + DL-alpha tocopheryl acetate + Doconexent + Folic acid + Heme iron polypeptide + Iron Dextran + Nicotinamide + Pantothenic acid + Potassium Iodide + Pyridoxine + Zinc oxide; parent_key: DB00893.", + "name: Menomune - A/c/y/w-135 Combined; ingredients: Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13889.", + "name: Advicor; ingredients: Lovastatin + Niacin; parent_key: DB00227.", + "name: Lovastatin-40; ingredients: Lovastatin; parent_key: DB00227.", + "name: Cholib; ingredients: Fenofibrate + Simvastatin; parent_key: DB00641.", + "name: Pro Hers Vanilla; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Biotin + Cholecalciferol + Choline + Chromium + Copper + Cyanocobalamin + Folic acid + Iodine + Manganese + Molybdenum + Niacin + Pantothenic acid + Phylloquinone + Pyridoxine + Riboflavin + Selenium + Thiamine + Zinc; parent_key: DB00122." + ] + }, + { + "example_idx": 110, + "anchor_id": 16543957595891420764, + "positive_id": 18352885729953710113, + "join_paths": [ + [ + 0, + 12, + 0.228515625 + ] + ], + "rows": [ + "Ranolazine: A Contemporary Review.", + "Angina, Stable\nAnimals\nCardiovascular Agents\nChronic Disease\nDrug Interactions\nDrug Labeling\nHumans\nOff-Label Use\nPractice Guidelines as Topic\nRanolazine\nSodium Channel Blockers\nTreatment Outcome" + ], + "sentences": [ + "ref-id: L2102; title: Zinc Therapy in Dermatology: A review ; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120804/; parent_key: DB01593.", + "ref-id: L1445; title: DORSET CARDIOLOGY WORKING GROUP GUIDELINE FOR CALCIUM CHANNEL BLOCKERS IN HYPERTENSION ; url: http://www.dorsetccg.nhs.uk/Downloads/aboutus/medicines-management/Other%20Guidelines/Calcium%20channel%20blockers%20for%20hypertension.pdf; parent_key: DB09235.", + "ref-id: L6742; title: FDA summary review; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761077Orig1s000SumR.pdf; parent_key: DB00373.", + "ref-id: L6802; title: FDA review, Eszopiclone; url: https://www.fda.gov/media/84679/download; parent_key: DB00402.", + "ref-id: L11043; title: FDA Approved Drug Products: Diflucan (fluconazole); url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019949s065,020090s047lbl.pdf; parent_key: DB00196.", + "ref-id: L6037; title: CADDRA - Canadian ADHD Practice Guidelines; url: https://www.caddra.ca/pdfs/caddraGuidelines2011.pdf; parent_key: DB00422.", + "ref-id: L1317; title: The effect of melperone, an atypical antipsychotic drug, on cognitive function in schizophrenia; url: https://www.sciencedirect.com/science/article/pii/S0920996401003292; parent_key: DB09224.", + "ref-id: L374; title: FDA Review- Telotristat ; url: http://www.lexpharma.com/media-center/news/525-fda-extends-pdufa-date-for-telotristat-etiprate-for-the-treatment-of-carcinoid-syndrome; parent_key: DB12095.", + "ref-id: L1618; title: Review of Rauwolfia; url: https://www.sciencedirect.com/topics/medicine-and-dentistry/rauvolfia-serpentina; parent_key: DB09363.", + "ref-id: L1425; title: Pharmacology review, Nitazoxanide; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-497_Alinia_Pharmr_P1.pdf; parent_key: DB00507.", + "ref-id: L2009; title: Vinorelbine FDA pharmacology review; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-388S008_Navelbine_biopharmr.pdf; parent_key: DB00361.", + "ref-id: L8192; title: Pharmacology review, FDA; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204820Orig1s000PharmR.pdf; parent_key: DB01394.", + "ref-id: L3580; title: Ranolazine FDA Label; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021526s007lbl.pdf; parent_key: DB00243.", + "ref-id: L2102; title: Zinc Therapy in Dermatology: A review ; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120804/; parent_key: DB14487.", + "ref-id: L2932; title: Avatrombopag Gains FDA Approval for Patients with Chronic Liver Disease; url: https://www.specialtypharmacytimes.com/news/avatrombopag-gains-fda-approval-for-patients-with-chronic-liver-disease; parent_key: DB11995.", + "ref-id: L2889; title: Review of Agkistrodon-Piscivorus; url: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/agkistrodon-piscivorus; parent_key: DB13893.", + "ref-id: L13670; title: FDA Summary Review: Empagliflozin; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000SumR.pdf; parent_key: DB09038.", + "ref-id: L7547; title: FDA application review, Trazodone; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022411s000MedR.pdf; parent_key: DB00656.", + "ref-id: L769; title: FDA Clinical Pharmacology and Biopharmaceutics Review; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000ClinPharmR.pdf; parent_key: DB11611.", + "ref-id: L162; title: Flockhart Table of Drug Interactions; url: https://drug-interactions.medicine.iu.edu/Main-Table.aspx; parent_key: DB00472.", + "ref-id: L2900; title: Significant Drug–Drug Interactions with Antineoplastics; url: https://www.ebi.ac.uk/chembl/target/inspect/CHEMBL1876; parent_key: DB00808.", + "ref-id: L2889; title: Review of Agkistrodon-Piscivorus; url: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/agkistrodon-piscivorus; parent_key: DB13894.", + "ref-id: L10905; title: Upadacitinib Summary Review - FDA; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211675Orig1s000SumR.pdf; parent_key: DB15091.", + "ref-id: L7994; title: FDA pharmacology review, Drospirenone; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022532Orig1s000PharmR.pdf; parent_key: DB01395.", + "ref-id: L10538; title: FDA Approved Drug Products: Cortenema Hydrocortisone Rectal Enema; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/016199s035lbl.pdf; parent_key: DB00741.", + "ref-id: L2727; title: Drugs@FDA: FDA Approved Drug Products; url: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=204114; parent_key: DB08911.", + "ref-id: L2243; title: FDA guidelines; url: https://www.fda.gov/downloads/Drugs/.../Guidances/ucm071320.pdf; parent_key: DB14007.", + "ref-id: L2636; title: Antiemetic, Neurokinin-1 Receptor Blockers; url: https://www.ncbi.nlm.nih.gov/books/NBK470394/; parent_key: DB14019.", + "ref-id: L2007; title: Vinorelbine, a clinical review; url: https://www.nature.com/articles/6691203.pdf?origin=ppub; parent_key: DB00361.", + "ref-id: L7691; title: ADA guidelines on fluoride use; url: https://www.ada.org/en/member-center/oral-health-topics/fluoride-topical-and-systemic-supplements; parent_key: DB09325.", + "ref-id: L13691; title: FDA Approved Drug Products: Spinraza (nusinersen) for intrathecal injection; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209531s007s008lbl.pdf; parent_key: DB13161.", + "ref-id: L1635; title: Cholecystokinin- a review; url: https://www.sciencedirect.com/topics/chemistry/cholecystokinin; parent_key: DB08862.", + "ref-id: L4166; title: FDA approves lusutrombopag for thrombocytopenia in adults with chronic liver disease; url: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm615348.htm; parent_key: DB13125.", + "ref-id: L2889; title: Review of Agkistrodon-Piscivorus; url: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/agkistrodon-piscivorus; parent_key: DB13891.", + "ref-id: L767; title: The Dermatology Review: Octinoxate; url: http://www.thedermreview.com/octinoxate/; parent_key: DB09496.", + "ref-id: L6481; title: FDA Approved Drug Products: Cipro Oral Suspension; url: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020780; parent_key: DB00537.", + "ref-id: L6133; title: FDA Approved Drug Products: Sinemet; url: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=017555; parent_key: DB01235.", + "ref-id: L9677; title: FDA Approved Drug Products: Vistaril (hydroxyzine pamoate); url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048,011795s025lbl.pdf; parent_key: DB00557.", + "ref-id: L6112; title: FDA Pharmacology Review: Exenatide; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021919s000pharmr.pdf; parent_key: DB01276.", + "ref-id: L258; title: drug label; url: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=43688; parent_key: DB09398.", + "ref-id: L6037; title: CADDRA - Canadian ADHD Practice Guidelines; url: https://www.caddra.ca/pdfs/caddraGuidelines2011.pdf; parent_key: DB00289.", + "ref-id: L6826; title: Pharmacology review, FDA; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210491Orig1s000PharmR.pdf; parent_key: DB11712.", + "ref-id: L10965; title: Angina: Mayo clinic; url: https://www.mayoclinic.org/diseases-conditions/angina/symptoms-causes/syc-20369373; parent_key: DB00243.", + "ref-id: L2822; title: FDA approves avatrombopag for thrombocytopenia in adults with chronic liver disease; url: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm608323.htm; parent_key: DB11995.", + "ref-id: L5897; title: U.S. FDA Approves INVOKANA® (canagliflozin) to Reduce the Risk of Heart Attack, Stroke or Cardiovascular Death in Adults with Type 2 Diabetes and Established Cardiovascular Disease; url: https://www.janssen.com/us-fda-approves-invokanar-canagliflozin-reduce-risk-heart-attack-stroke-or-cardiovascular-death; parent_key: DB08907.", + "ref-id: L2827; title: Polivinyl Alcohol Review; url: https://www.omicsonline.org/open-access/polyvinyl-alcohol-in-medicine-and-pharmacy-a-perspective-2329-6631.1000112.php?aid=21700; parent_key: DB11060.", + "ref-id: L2437; title: European Food Safety Authority (EFSA): Copper(II) oxide as a source of copper added for nutritional purposes; url: https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2009.1089; parent_key: DB11134.", + "ref-id: L6487; title: FDA Approved Drug Products: Cipro XR Extended Release Tablet; url: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021554; parent_key: DB00537.", + "ref-id: L162; title: Flockhart Table of Drug Interactions; url: https://drug-interactions.medicine.iu.edu/Main-Table.aspx; parent_key: DB00404.", + "ref-id: L11461; title: Diabetes Canada: Clinical Practice Guidelines for Diabetes 2018; url: http://guidelines.diabetes.ca/docs/CPG-2018-full-EN.pdf; parent_key: DB01132." + ] + }, + { + "example_idx": 111, + "anchor_id": 14220417608703520152, + "positive_id": 18254678658480857161, + "join_paths": [ + [ + 0, + 46, + 0.287109375 + ], + [ + 0, + 41, + 0.283203125 + ], + [ + 2, + 4, + 0.27734375 + ], + [ + 2, + 46, + 0.2734375 + ], + [ + 6, + 4, + 0.271484375 + ] + ], + "rows": [ + "Several metabolites of tamoxifen, including 4-hydroxy-N-desmethyltamoxifen (metabolite BX), 4-hydroxytamoxifen (metabolite B), N-desmethyltamoxifen (metabolite X), the primary alcohol (metabolite Y), and N-desdimethyltamoxifen (metabolite Z) were identified and their concentrations determined in fluids and feces from patients receiving chronic tamoxifen treatment.", + "The biological samples investigated were serum, pleural, pericardial and peritoneal effusions, cerebrospinal fluid, saliva, bile, feces, and urine.", + "In serum, tamoxifen itself, and the metabolites X and Z were the prevailing species, but significant amounts of the metabolites Y, B, and BX were also detected.", + "About 3 h after drug intake tamoxifen as well as Y, B, BX, X, and Z showed a peak in serum.", + "This may be explained by efficient metabolism of the metabolite precursor before being distributed to peripheral compartments.", + "Upon drug withdrawal all metabolites showed first-order elimination curves which paralleled that of tamoxifen suggesting that their rate of elimination exceeded that of tamoxifen and that the serum levels are production rate limited.", + "The protein binding of tamoxifen and its major serum metabolites (Y, X, Z) was determined and found to be higher than 98%.", + "Albumin was the predominant carrier for tamoxifen in human plasma.", + "The concentrations of tamoxifen and its metabolites in pleural, pericardial, and peritoneal effusions equalled those detected in serum, corresponding to an effusion/serum ratio between 0.2 and 1.", + "Only trace amounts of tamoxifen and metabolite X were detected in cerebrospinal fluid (CSF/serum ratio less than 0.02).", + "In saliva, concentrations of tamoxifen and X exceeded the amounts of free drug in serum, suggesting active transport or trapping of these compounds in the salivary gland.", + "Bile and urine were rich in the hydroxylated, conjugated metabolites (Y, B, and BX), whereas in feces unconjugated metabolite B and tamoxifen were the predominating species.", + "Adult\nAged\nAscitic Fluid\nBlood Proteins\nBody Fluids\nFemale\nHumans\nMiddle Aged\nPericardial Effusion\nPleural Effusion\nProtein Binding\nSaliva\nTamoxifen" + ], + "sentences": [ + "name: Apo-tamox Tab 10mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Human Albumin Grifols 20%; ingredients: Albumin human; parent_key: DB00062.", + "name: Soltamox; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Tamone - (10 Mg); ingredients: Tamoxifen; parent_key: DB00675.", + "name: Dom-tamoxifen; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Albutein 25% Soln USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Sterile Diluent for Allergenic Extract; ingredients: Albumin human + Phenol; parent_key: DB00062.", + "name: Octalbin 25%; ingredients: Albumin human; parent_key: DB00062.", + "name: Albumin (human) 5% Solution; ingredients: Albumin human; parent_key: DB00062.", + "name: Albutein 5% Soln USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuminex; ingredients: Albumin human; parent_key: DB00062.", + "name: Plasma Protein Fraction (human) Protenate; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Buminate 5%; ingredients: Albumin human; parent_key: DB00062.", + "name: Diluent for Allergenic Extract Sterile Albumin Saline With Phenol; ingredients: Albumin human; parent_key: DB00062.", + "name: Grizzly Creek Naturals Sanitizer Huckleberry; ingredients: Isopropyl alcohol; parent_key: DB02325.", + "name: Albumin Human Diluent; ingredients: Albumin human + Sodium chloride; parent_key: DB00062.", + "name: 4052 First Aid Kit; ingredients: Benzalkonium + Ethanol + Isopropyl alcohol + Lidocaine + Lidocaine + Neomycin; parent_key: DB00898.", + "name: Plasmanate; ingredients: Albumin human; parent_key: DB00062.", + "name: Albutein; ingredients: Albumin human; parent_key: DB00062.", + "name: Octalbin 5%; ingredients: Albumin human; parent_key: DB00062.", + "name: 4310 First Aid Kit; ingredients: Acetaminophen + Benzalkonium + Ethanol + Isopropyl alcohol + Lidocaine + Neomycin + Water; parent_key: DB00281.", + "name: Tamone - (20 Mg); ingredients: Tamoxifen; parent_key: DB00675.", + "name: PMS-tamoxifen; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Volumex; ingredients: Albumin iodinated I-131 serum; parent_key: DB09430.", + "name: Albumin (human) 25% Solution USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Flexbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Nolvadex Tab 10mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Optison; ingredients: Albumin human; parent_key: DB00062.", + "name: 4287 First Aid Kit; ingredients: Acetaminophen + Bacitracin + Isopropyl alcohol + Neomycin + Polymyxin B + Water; parent_key: DB00994.", + "name: Albuked; ingredients: Albumin human; parent_key: DB00062.", + "name: Plasbumin-25; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuminar-25; ingredients: Albumin human; parent_key: DB00062.", + "name: Pancreatin and Enzyme Formula - Tablet; ingredients: Bromelains + Ox bile extract + Pancrelipase + Pancrelipase lipase + Pepsin; parent_key: DB13198.", + "name: Helios Hand Sanitizer; ingredients: Isopropyl alcohol; parent_key: DB02325.", + "name: CVS All Purpose First Aid Kit; ingredients: Acetaminophen + Acetylsalicylic acid + Ammonia + Bacitracin + Benzalkonium + Ibuprofen + Isopropyl alcohol + Lidocaine + Neomycin + Polymyxin B; parent_key: DB00945.", + "name: Plasbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Nolvadex-D Tab 20mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Nolvadex; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Tamoplex Tab 20mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Buminate 25%; ingredients: Albumin human; parent_key: DB00062.", + "name: Teva-tamoxifen; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Tamoxifene - 10; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Sol-M Alcohol Swabs Medium Non-Sterile; ingredients: Isopropyl alcohol; parent_key: DB02325.", + "name: Albumin (human) 5% Solution, USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Tamone Tab 20mg; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Octaplasma; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Tamoxifene - 20; ingredients: Tamoxifen; parent_key: DB00675.", + "name: Afluria; ingredients: Influenza A virus A/California/7/2009 X-181 (H1N1) antigen (propiolactone inactivated) + Influenza A virus A/Victoria/361/2011 IVR-165 (H3N2) antigen (propiolactone inactivated) + Influenza B virus B/Hubei-Wujiagang/158/2009 BX-39 antigen (propiolactone inactivated); parent_key: DB10600.", + "name: First Aid Value Pack - 77 Pieces; ingredients: Bacitracin + Benzalkonium + Benzalkonium + Isopropyl alcohol + Lidocaine + Neomycin + Polymyxin B; parent_key: DB11105.", + "name: Albuminar-20; ingredients: Albumin human; parent_key: DB00062." + ] + }, + { + "example_idx": 112, + "anchor_id": 1858508112515433532, + "positive_id": 8868022005184057142, + "join_paths": [ + [ + 0, + 26, + 0.337890625 + ], + [ + 0, + 40, + 0.333984375 + ], + [ + 0, + 35, + 0.31640625 + ], + [ + 0, + 34, + 0.314453125 + ], + [ + 0, + 37, + 0.3125 + ] + ], + "rows": [ + "Background The misnamed 'vitamin' D is actually the hormone calcitriol (1,25 dihydroxyhydroxyvitamin D).", + "It has a central regulatory role in calcium metabolism, and more widely in the immune system.", + "The prohormone calcifediol (25 hydroxyvitamin D) is more easily measured in the laboratory and is the analyte used in reference interval formulation.", + "Being highly lipid soluble, both calcifediol and calcitriol travel in the bloodstream on carriage proteins, principally on vitamin D-binding protein.", + "Summary This review reports our current understanding of vitamin D-binding protein.", + "Its genetic determinants and their effect on it and secondarily on calcifediol concentrations and assays are described.", + "Its complex interplay with parathyroid hormone is considered.", + "The analytical state of the art is translated into the challenge it imposes clinically, in the formulation of reference intervals and in their use in advising and managing patients.", + "Several recent challenges thrown up to laboratories by percipient clinicians highlight the dilemma vitamin D-binding protein poses.", + "A way forward is suggested.", + "Calcifediol\nCalcitriol\nCalcium\nChromatography, Liquid\nGene Expression Regulation\nHumans\nImmunoassay\nParathyroid Hormone\nReference Values\nTandem Mass Spectrometry\nVitamin D\nVitamin D Deficiency\nVitamin D-Binding Protein" + ], + "sentences": [ + "drugbank-id: DB05829; name: Parathyroid hormone; description: The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Pamidronic acid.; parent_key: DB00282.", + "drugbank-id: DB05829; name: Parathyroid hormone; description: The risk or severity of adverse effects can be increased when Diethylpropion is combined with Parathyroid hormone.; parent_key: DB00937.", + "drugbank-id: DB01509; name: Tenamfetamine; description: The risk or severity of adverse effects can be increased when Tenamfetamine is combined with Parathyroid hormone.; parent_key: DB05829.", + "drugbank-id: DB00163; name: Vitamin E; description: Vitamin E may increase the anticoagulant activities of (R)-warfarin.; parent_key: DB08496.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Vandetanib can be increased when combined with Vitamin E.; parent_key: DB05294.", + "drugbank-id: DB00672; name: Chlorpropamide; description: The therapeutic efficacy of Chlorpropamide can be decreased when used in combination with Goserelin.; parent_key: DB00014.", + "drugbank-id: DB10353; name: Poa annua pollen; description: The risk of a hypersensitivity reaction to Poa annua pollen is increased when it is combined with Landiolol.; parent_key: DB12212.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Sirolimus can be increased when combined with Vitamin E.; parent_key: DB00877.", + "drugbank-id: DB00208; name: Ticlopidine; description: The metabolism of Ticlopidine can be increased when combined with Infliximab.; parent_key: DB00065.", + "drugbank-id: DB00821; name: Carprofen; description: The protein binding of Carbutamide can be decreased when combined with Carprofen.; parent_key: DB13406.", + "drugbank-id: DB01017; name: Minocycline; description: Minocycline may increase the central nervous system depressant (CNS depressant) activities of Valproic acid.; parent_key: DB00313.", + "drugbank-id: DB00163; name: Vitamin E; description: Vitamin E may increase the anticoagulant activities of Fluindione.; parent_key: DB13136.", + "drugbank-id: DB04849; name: Cediranib; description: The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Cediranib.; parent_key: DB05829.", + "drugbank-id: DB05829; name: Parathyroid hormone; description: The risk or severity of adverse effects can be increased when Fenoterol is combined with Parathyroid hormone.; parent_key: DB01288.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Cyproterone acetate can be increased when combined with Vitamin E.; parent_key: DB04839.", + "drugbank-id: DB00162; name: Vitamin A; description: The therapeutic efficacy of Demegestone can be decreased when used in combination with Vitamin A.; parent_key: DB13857.", + "drugbank-id: DB00162; name: Vitamin A; description: The therapeutic efficacy of Ethinylestradiol can be decreased when used in combination with Vitamin A.; parent_key: DB00977.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Cytarabine can be decreased when combined with Vitamin D.; parent_key: DB00987.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Tamoxifen can be increased when combined with Vitamin E.; parent_key: DB00675.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Vitamin D can be decreased when combined with Voriconazole.; parent_key: DB00582.", + "drugbank-id: DB01401; name: Choline magnesium trisalicylate; description: The risk or severity of hypertension, hyponatremia, and water intoxication can be increased when Choline magnesium trisalicylate is combined with Desmopressin.; parent_key: DB00035.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Norelgestromin can be increased when combined with Vitamin E.; parent_key: DB06713.", + "drugbank-id: DB00163; name: Vitamin E; description: Vitamin E may increase the anticoagulant activities of Gabexate.; parent_key: DB12831.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Gossypol can be increased when combined with Vitamin E.; parent_key: DB13044.", + "drugbank-id: DB05829; name: Parathyroid hormone; description: The risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Ouabain.; parent_key: DB01092.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Testosterone enanthate can be increased when combined with Vitamin E.; parent_key: DB13944.", + "drugbank-id: DB11094; name: Vitamin D; description: The therapeutic efficacy of Vitamin D can be decreased when used in combination with Dexamethasone.; parent_key: DB01234.", + "drugbank-id: DB00865; name: Benzphetamine; description: The risk or severity of adverse effects can be increased when Benzphetamine is combined with Parathyroid hormone.; parent_key: DB05829.", + "drugbank-id: DB11094; name: Vitamin D; description: The therapeutic efficacy of Vitamin D can be decreased when used in combination with Fluperolone.; parent_key: DB13491.", + "drugbank-id: DB00450; name: Droperidol; description: Droperidol may increase the central nervous system depressant (CNS depressant) activities of Zolmitriptan.; parent_key: DB00315.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Vitamin D can be increased when combined with Lansoprazole.; parent_key: DB00448.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Demegestone can be increased when combined with Vitamin E.; parent_key: DB13857.", + "drugbank-id: DB00163; name: Vitamin E; description: Vitamin E may increase the antiplatelet activities of Nitroaspirin.; parent_key: DB12445.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Vitamin D can be decreased when combined with Bryostatin 1.; parent_key: DB11752.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Vitamin D can be decreased when combined with Vinblastine.; parent_key: DB00570.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Vitamin D can be decreased when combined with Pasireotide.; parent_key: DB06663.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Albendazole can be increased when combined with Vitamin E.; parent_key: DB00518.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Vitamin D can be increased when combined with Infliximab.; parent_key: DB00065.", + "drugbank-id: DB00163; name: Vitamin E; description: Vitamin E may increase the anticoagulant activities of Fibrinolysin.; parent_key: DB05254.", + "drugbank-id: DB09015; name: Canrenoic acid; description: Canrenoic acid may increase the excretion rate of Lorazepam which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB00186.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Vitamin D can be decreased when combined with Lanreotide.; parent_key: DB06791.", + "drugbank-id: DB05829; name: Parathyroid hormone; description: The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Dapoxetine.; parent_key: DB04884.", + "drugbank-id: DB08976; name: Floctafenine; description: The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Valsartan is combined with Floctafenine.; parent_key: DB00177.", + "drugbank-id: DB01077; name: Etidronic acid; description: The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Etidronic acid.; parent_key: DB05829.", + "drugbank-id: DB00322; name: Floxuridine; description: The risk or severity of bleeding can be increased when Alteplase is combined with Floxuridine.; parent_key: DB00009.", + "drugbank-id: DB00163; name: Vitamin E; description: The metabolism of Isavuconazole can be increased when combined with Vitamin E.; parent_key: DB11633.", + "drugbank-id: DB00472; name: Fluoxetine; description: The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Fluoxetine.; parent_key: DB05829.", + "drugbank-id: DB11094; name: Vitamin D; description: The metabolism of Vitamin D can be decreased when combined with Fluvastatin.; parent_key: DB01095.", + "drugbank-id: DB00163; name: Vitamin E; description: Vitamin E may increase the anticoagulant activities of Reviparin.; parent_key: DB09259.", + "drugbank-id: DB05829; name: Parathyroid hormone; description: The risk or severity of adverse effects can be increased when Norepinephrine is combined with Parathyroid hormone.; parent_key: DB00368." + ] + }, + { + "example_idx": 113, + "anchor_id": 12442019129934653160, + "positive_id": 17538331461754680418, + "join_paths": [ + [ + 0, + 24, + 0.23046875 + ], + [ + 0, + 31, + 0.23046875 + ], + [ + 0, + 37, + 0.2265625 + ], + [ + 0, + 11, + 0.22265625 + ], + [ + 0, + 5, + 0.20703125 + ] + ], + "rows": [ + "Lamotrigine (an epileptic drug) interaction with human serum albumin (HSA) was investigated by fluorescence, UV-Vis, FTIR, CD spectroscopic techniques, and molecular modeling methods.", + "Binding constant (K\nAnticonvulsants\nHumans\nHydrogen Bonding\nLamotrigine\nModels, Molecular\nSerum Albumin\nSpectrum Analysis\nTriazines" + ], + "sentences": [ + "name: Lamictal - Tab 200mg; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Plasmanate; ingredients: Albumin human; parent_key: DB00062.", + "name: Subvenite; ingredients: Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: Volumex; ingredients: Albumin iodinated I-131 serum; parent_key: DB09430.", + "name: Ratio-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Lamotrigine-100; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Gardasil 9; ingredients: Human papillomavirus type 11 L1 capsid protein antigen + Human papillomavirus type 16 L1 capsid protein antigen + Human papillomavirus type 18 L1 capsid protein antigen + Human papillomavirus type 31 L1 capsid protein antigen + Human papillomavirus type 33 L1 capsid protein antigen + Human papillomavirus type 45 L1 capsid protein antigen + Human papillomavirus type 52 L1 capsid protein antigen + Human papillomavirus type 58 L1 capsid protein antigen + Human papillomavirus type 6 L1 capsid protein antigen; parent_key: DB10310.", + "name: Lamotrigine Extended Release; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Albumin (Human); ingredients: Albumin human; parent_key: DB00062.", + "name: Albuked; ingredients: Albumin human; parent_key: DB00062.", + "name: Lamictal XR; ingredients: Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: Lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Lamictal XR; ingredients: Lamotrigine + Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: Jeanatope; ingredients: Albumin iodinated I-125 serum; parent_key: DB09429.", + "name: Lamictal XR; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Subvenite; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Carimune Nanofiltered; ingredients: Human immunoglobulin G; parent_key: DB00028.", + "name: AlbuRx; ingredients: Albumin human; parent_key: DB00062.", + "name: Auro-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Apo-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Human Albumin Grifols; ingredients: Albumin human; parent_key: DB00062.", + "name: Plasbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Lamictal ODT; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Teva-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Lamotrigine; ingredients: Lamotrigine + Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: Quixil; ingredients: Calcium chloride + Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: Mylan-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Orajel Antiseptic Rinse for Mouth Sores; ingredients: Hydrogen peroxide; parent_key: DB11091.", + "name: Kedbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Lamictal ODT; ingredients: Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: Gamunex; ingredients: Human immunoglobulin G; parent_key: DB00028.", + "name: Lamotrigine; ingredients: Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: Flulaval Quadrivalent 2017/2018; ingredients: Influenza A virus A/Hong Kong/4801/2014 X-263B (H3N2) antigen (UV, formaldehyde inactivated) + Influenza A virus A/Singapore/GP1908/2015 IVR-180 (H1N1) antigen (UV, formaldehyde inactivated) + Influenza B virus B/Brisbane/60/2008 antigen (UV, formaldehyde inactivated) + Influenza B virus B/Phuket/3073/2013 antigen (UV, formaldehyde inactivated); parent_key: DB10599.", + "name: Hyperrho S/d Mini-dose; ingredients: Human Rho(D) immune globulin; parent_key: DB11597.", + "name: PMS-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Lamictal; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Lamictal ODT; ingredients: Lamotrigine + Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: LAMOTRIGINE Kit; ingredients: Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: Dom-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Panzyga; ingredients: Human immunoglobulin G; parent_key: DB00028.", + "name: PHL-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Flexbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Lamotrigine-150; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Megatope; ingredients: Albumin iodinated I-131 serum; parent_key: DB09430.", + "name: Lamictal; ingredients: Lamotrigine + Lamotrigine; parent_key: DB00555.", + "name: T.R.U.E. Test Thin-Layer Rapid Use Patch Test; ingredients: 2-mercaptobenzothiazole + 2,2'-Dibenzothiazyl disulfide + 4-(Isopropylamino)diphenylamine + alpha-Amyl cinnamaldehyde + Bacitracin + Balsam of Peru + Benzocaine + Benzylparaben + Bisphenol A diglycidyl ether + Bromothalonil + Bronopol + Budesonide + Butylparaben + Chlorquinaldol + Cinchocaine + Cinnamaldehyde + Cinnamyl alcohol + Clioquinol + Cobalt chloride + Diazolidinylurea + Dichromate + Dipentamethylenethiuram disulfide + Diphenylguanidine + Disperse Blue 106 + Disulfiram + Ditiocarb zinc + Ethyl hydroxybenzoate + Ethylenediamine + Eugenol + Evernia prunastri + Formaldehyde + Geraniol + Hydrocortisone butyrate + Hydroxycitronellal + Imidurea + Isoeugenol + Lanolin alcohols + Methylchloroisothiazolinone + Methylparaben + Morpholinylmercaptobenzothiazole + N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine + N,N'-diphenyl-1,4-phenylenediamine + Neomycin + Nickel sulfate + p-Phenylenediamine + P-Tert-Butylphenol-Formaldehyde Resin (Low Molecular Weight) + Parthenolide + Propylparaben + Quaternium-15 + Rosin + Sodium aurotiosulfate + Tetracaine + Tetramethylthiuram monosulfide + Thimerosal + Thiohexam + Thiram + Tixocortol + Zinc dibutyldithiocarbamate; parent_key: DB14191.", + "name: Albutein; ingredients: Albumin human; parent_key: DB00062.", + "name: Humulin 40/60 Inj; ingredients: Insulin human + Insulin human; parent_key: DB00030.", + "name: Nu-lamotrigine; ingredients: Lamotrigine; parent_key: DB00555.", + "name: Lamotrigine-25; ingredients: Lamotrigine; parent_key: DB00555." + ] + }, + { + "example_idx": 114, + "anchor_id": 11405327763949339645, + "positive_id": 3575758043120187468, + "join_paths": [ + [ + 3, + 21, + 0.1650390625 + ], + [ + 3, + 45, + 0.1630859375 + ], + [ + 3, + 47, + 0.1630859375 + ], + [ + 3, + 38, + 0.1533203125 + ], + [ + 3, + 46, + 0.150390625 + ] + ], + "rows": [ + "The melastatin-related transient receptor potential (TRP) channel TRPM3 is a nonselective cation channel expressed in nociceptive neurons and activated by heat.", + "Because TRPM3-deficient mice show inflammatory thermal hyperalgesia, pharmacological inhibition of TRPM3 may exert antinociceptive properties.", + "Fluorometric Ca influx assays and a compound library containing approved or clinically tested drugs were used to identify TRPM3 inhibitors.", + "Biophysical properties of channel inhibition were assessed using electrophysiological methods.", + "The nonsteroidal anti-inflammatory drug diclofenac, the tetracyclic antidepressant maprotiline, and the anticonvulsant primidone were identified as highly efficient TRPM3 blockers with half-maximal inhibition at 0.6 to 6 μM and marked specificity for TRPM3.", + "Most prominently, primidone was biologically active to suppress TRPM3 activation by pregnenolone sulfate (PregS) and heat at concentrations markedly lower than plasma concentrations commonly used in antiepileptic therapy.", + "Primidone blocked PregS-induced Cai influx through TRPM3 by allosteric modulation and reversibly inhibited atypical inwardly rectifying TRPM3 currents induced by coapplication of PregS and clotrimazole.", + "In vivo, analgesic effects of low doses of primidone were demonstrated in mice, applying PregS- and heat-induced pain models, including inflammatory hyperalgesia.", + "Thus, applying the approved drug at concentrations that are lower than those needed to induce anticonvulsive effects offers a shortcut for studying physiological and pathophysiological roles of TRPM3 in vivo.", + "Adrenergic Uptake Inhibitors\nAnalgesics\nAnimals\nAnti-Inflammatory Agents, Non-Steroidal\nCalcium\nDiclofenac\nDisease Models, Animal\nDose-Response Relationship, Drug\nGanglia, Spinal\nHEK293 Cells\nHumans\nHyperalgesia\nMale\nMaprotiline\nMembrane Potentials\nMice\nMice, Inbred C57BL\nNeurons\nPain\nPain Threshold\nPatch-Clamp Techniques\nPregnenolone\nPrimidone\nRats\nTRPM Cation Channels" + ], + "sentences": [ + "id: BE0005112; name: Transient receptor potential cation channel subfamily V member 5; organism: Humans; known_action: no; position: 5; parent_key: DB11093.", + "id: BE0005126; name: Transient receptor potential cation channel subfamily M member 6; organism: Humans; known_action: unknown; position: 3; parent_key: DB14513.", + "id: BE0005102; name: Transient receptor potential cation channel subfamily V member 6; organism: Humans; known_action: no; position: 1; parent_key: DB11093.", + "id: BE0004907; name: 5'-AMP-activated protein kinase; organism: Humans; known_action: unknown; position: 13; parent_key: DB00273.", + "id: BE0005295; name: Ryanodine receptor 2; organism: Humans; known_action: unknown; position: 39; parent_key: DB11093.", + "id: BE0003649; name: High affinity copper uptake protein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00526.", + "id: BE0005112; name: Transient receptor potential cation channel subfamily V member 5; organism: Humans; known_action: no; position: 10; parent_key: DB11348.", + "id: BE0003662; name: Probable low affinity copper uptake protein 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB00515.", + "id: BE0004624; name: Transient receptor potential cation channel subfamily M member 7; organism: Humans; known_action: no; position: 4; parent_key: DB09481.", + "id: BE0005296; name: Ryanodine receptor 3; organism: Humans; known_action: unknown; position: 43; parent_key: DB11093.", + "id: BE0008718; name: Voltage-dependent R-type calcium channel; organism: Humans; known_action: unknown; position: 54; parent_key: DB11348.", + "id: BE0003657; name: Multidrug and toxin extrusion protein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB01137.", + "id: BE0005102; name: Transient receptor potential cation channel subfamily V member 6; organism: Humans; known_action: no; position: 6; parent_key: DB11348.", + "id: BE0003657; name: Multidrug and toxin extrusion protein 1; organism: Humans; known_action: unknown; position: 6; parent_key: DB04574.", + "id: BE0002083; name: Sodium channel protein type 4 subunit alpha; organism: Humans; known_action: unknown; position: 15; parent_key: DB00586.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB01017.", + "id: BE0005126; name: Transient receptor potential cation channel subfamily M member 6; organism: Humans; known_action: no; position: 1; parent_key: DB09481.", + "id: BE0004752; name: Multidrug and toxin extrusion protein 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB11652.", + "id: BE0004752; name: Multidrug and toxin extrusion protein 2; organism: Humans; known_action: unknown; position: 16; parent_key: DB12267.", + "id: BE0000353; name: Acid-sensing ion channel 1; organism: Humans; known_action: unknown; position: 16; parent_key: DB00586.", + "id: BE0008716; name: Voltage-dependent T-type calcium channel; organism: Humans; known_action: unknown; position: 48; parent_key: DB11093.", + "id: BE0008715; name: Voltage-dependent L-type calcium channel; organism: Humans; known_action: unknown; position: 51; parent_key: DB11348.", + "id: BE0005102; name: Transient receptor potential cation channel subfamily V member 6; organism: Humans; known_action: no; position: 42; parent_key: DB14481.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: no; position: 1; parent_key: DB13092.", + "id: BE0008714; name: Cation channel sperm-associated protein 1; organism: Humans; known_action: unknown; position: 50; parent_key: DB11348.", + "id: BE0008714; name: Cation channel sperm-associated protein 1; organism: Humans; known_action: unknown; position: 45; parent_key: DB11093.", + "id: BE0003657; name: Multidrug and toxin extrusion protein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB08840.", + "id: BE0008718; name: Voltage-dependent R-type calcium channel; organism: Humans; known_action: unknown; position: 54; parent_key: DB14481.", + "id: BE0005112; name: Transient receptor potential cation channel subfamily V member 5; organism: Humans; known_action: no; position: 44; parent_key: DB14481.", + "id: BE0003662; name: Probable low affinity copper uptake protein 2; organism: Humans; known_action: unknown; position: 27; parent_key: DB09130.", + "id: BE0004752; name: Multidrug and toxin extrusion protein 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB11732.", + "id: BE0008718; name: Voltage-dependent R-type calcium channel; organism: Humans; known_action: unknown; position: 49; parent_key: DB11093.", + "id: BE0008714; name: Cation channel sperm-associated protein 1; organism: Humans; known_action: unknown; position: 50; parent_key: DB14481.", + "id: BE0000942; name: Low-density lipoprotein receptor-related protein 2; organism: Humans; known_action: unknown; position: 13; parent_key: DB00115.", + "id: BE0008717; name: Voltage-dependent P/Q-type calcium channel; organism: Humans; known_action: unknown; position: 52; parent_key: DB14481.", + "id: BE0000090; name: Potassium voltage-gated channel subfamily H member 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB12364.", + "id: BE0000189; name: Scavenger receptor class B member 1; organism: Humans; known_action: unknown; position: 8; parent_key: DB00163.", + "id: BE0002196; name: Amine oxidase [flavin-containing] B; organism: Humans; known_action: unknown; position: 3; parent_key: DB12612.", + "id: BE0008716; name: Voltage-dependent T-type calcium channel; organism: Humans; known_action: unknown; position: 53; parent_key: DB11348.", + "id: BE0004624; name: Transient receptor potential cation channel subfamily M member 7; organism: Humans; known_action: unknown; position: 4; parent_key: DB14513.", + "id: BE0000739; name: Ryanodine receptor 1; organism: Humans; known_action: unknown; position: 38; parent_key: DB11093.", + "id: BE0000940; name: Sodium- and chloride-dependent glycine transporter 1; organism: Humans; known_action: unknown; position: 30; parent_key: DB00145.", + "id: BE0008717; name: Voltage-dependent P/Q-type calcium channel; organism: Humans; known_action: unknown; position: 52; parent_key: DB11348.", + "id: BE0009808; name: Transient receptor potential cation channel subfamily M member 3; organism: Humans; known_action: unknown; position: 14; parent_key: DB00794.", + "id: BE0008717; name: Voltage-dependent P/Q-type calcium channel; organism: Humans; known_action: unknown; position: 47; parent_key: DB11093.", + "id: BE0008715; name: Voltage-dependent L-type calcium channel; organism: Humans; known_action: unknown; position: 51; parent_key: DB14481.", + "id: BE0008716; name: Voltage-dependent T-type calcium channel; organism: Humans; known_action: unknown; position: 53; parent_key: DB14481.", + "id: BE0008715; name: Voltage-dependent L-type calcium channel; organism: Humans; known_action: unknown; position: 46; parent_key: DB11093.", + "id: BE0003657; name: Multidrug and toxin extrusion protein 1; organism: Humans; known_action: unknown; position: 9; parent_key: DB12332.", + "id: BE0003662; name: Probable low affinity copper uptake protein 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00958." + ] + }, + { + "example_idx": 115, + "anchor_id": 13562576807761836955, + "positive_id": 4819622613940312605, + "join_paths": [ + [ + 7, + 6, + 0.3359375 + ], + [ + 3, + 6, + 0.333984375 + ], + [ + 3, + 33, + 0.32421875 + ], + [ + 7, + 12, + 0.32421875 + ], + [ + 0, + 6, + 0.322265625 + ] + ], + "rows": [ + "Oxcarbazepine is indicated for the treatment of partial or generalised tonic-clonic seizures.", + "Most of the absorbed oxcarbazepine is converted into its active metabolite, 10-hydroxycarbazepine (MHD), which can exist as R-(-)- and S-(+)-MHD enantiomers.", + "Here we describe the influence of the P-glycoprotein (P-gp) inhibitor verapamil, on the disposition of oxcarbazepine and MHD enantiomers, both of which are P-gp substrates.", + "Healthy subjects (n=12) were randomised to oxcarbazepine or oxcarbazepine combined with verapamil at doses of 300mg b.i.d.", + "and 80mg t.i.d., respectively.", + "Blood samples (n=185) were collected over a period of 12h post oxcarbazepine dose.", + "An integrated PK model was developed using nonlinear mixed effects modelling using a meta-analytical approach.", + "The pharmacokinetics of oxcarbazepine was described by a two-compartment model with absorption transit compartments and first-order elimination.", + "The concentration-time profiles of both MHD enantiomers were characterised by a one-compartment distribution model.", + "Clearance estimates (95% CI) were 84.9L/h (69.5-100.3) for oxcarbazepine and 2.0L/h (1.9-2.1) for both MHD enantiomers.", + "The volume of distribution was much larger for oxcarbazepine (131L (97-165)) as compared to R-(-)- and S-(+)-MHD (23.6L (14.4-32.8) vs. 31.7L (22.5-40.9), respectively).", + "Co-administration of verapamil resulted in a modest increase of the apparent bioavailability of oxcarbazepine by 12% (10-28), but did not affect parent or metabolite clearances.", + "Despite the evidence of comparable systemic levels of OXC and MHD following administration of verapamil, differences in brain exposure to both moieties cannot be excluded after P-glycoprotein inhibition.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAdult\nAnticonvulsants\nBiological Availability\nCarbamazepine\nCross-Over Studies\nFemale\nHealthy Volunteers\nHumans\nMale\nOxcarbazepine\nSeizures\nStereoisomerism\nVerapamil\nYoung Adult" + ], + "sentences": [ + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Aprepitant can be increased when combined with Oxcarbazepine.; parent_key: DB00673.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: Oxcarbazepine may increase the excretion rate of Dyphylline which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB00651.", + "drugbank-id: DB06807; name: Phenyl aminosalicylate; description: The risk or severity of bleeding can be increased when Phenyl aminosalicylate is combined with Lepirudin.; parent_key: DB00001.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Ramelteon can be decreased when combined with Oxcarbazepine.; parent_key: DB00980.", + "drugbank-id: DB00661; name: Verapamil; description: Indobufen may decrease the excretion rate of Verapamil which could result in a higher serum level.; parent_key: DB12545.", + "drugbank-id: DB13257; name: Ferrous sulfate anhydrous; description: Ranitidine can cause a decrease in the absorption of Ferrous sulfate anhydrous resulting in a reduced serum concentration and potentially a decrease in efficacy.; parent_key: DB00863.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: Oxcarbazepine may increase the central nervous system depressant (CNS depressant) activities of Nicardipine.; parent_key: DB00622.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Elbasvir can be increased when combined with Oxcarbazepine.; parent_key: DB11574.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Pyrantel.; parent_key: DB11156.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Cobicistat can be increased when combined with Oxcarbazepine.; parent_key: DB09065.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Paritaprevir can be increased when combined with Oxcarbazepine.; parent_key: DB09297.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Fencamfamin.; parent_key: DB01463.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: Oxcarbazepine may increase the central nervous system depressant (CNS depressant) activities of Benzilone.; parent_key: DB13369.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Iprindole.; parent_key: DB13496.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Perazine.; parent_key: DB12710.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Penbutolol.; parent_key: DB01359.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Amprenavir can be increased when combined with Oxcarbazepine.; parent_key: DB00701.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: Oxcarbazepine may increase the central nervous system depressant (CNS depressant) activities of Nortriptyline.; parent_key: DB00540.", + "drugbank-id: DB08836; name: Temocapril; description: The risk or severity of angioedema can be increased when Alteplase is combined with Temocapril.; parent_key: DB00009.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Quinine can be increased when combined with Oxcarbazepine.; parent_key: DB00468.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Cetirizine is combined with Oxcarbazepine.; parent_key: DB00341.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Paclitaxel can be increased when combined with Oxcarbazepine.; parent_key: DB01229.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Clorindione can be increased when combined with Oxcarbazepine.; parent_key: DB13275.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The serum concentration of Selpercatinib can be decreased when it is combined with Oxcarbazepine.; parent_key: DB15685.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Methylpentynol.; parent_key: DB13733.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Eplerenone can be increased when combined with Oxcarbazepine.; parent_key: DB00700.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: Oxcarbazepine may increase the excretion rate of PCS-499 which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB15122.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Piritramide.; parent_key: DB12492.", + "drugbank-id: DB08455; name: Ro 12-7310; description: The therapeutic efficacy of Chlormadinone can be decreased when used in combination with Ro 12-7310.; parent_key: DB13528.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Xylazine.; parent_key: DB11477.", + "drugbank-id: DB13650; name: Aloglutamol; description: Naproxen can cause a decrease in the absorption of Aloglutamol resulting in a reduced serum concentration and potentially a decrease in efficacy.; parent_key: DB00788.", + "drugbank-id: DB01142; name: Doxepin; description: Doxepin can cause a decrease in the absorption of Indinavir resulting in a reduced serum concentration and potentially a decrease in efficacy.; parent_key: DB00224.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Minaprine.; parent_key: DB00805.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Phenibut.; parent_key: DB13455.", + "drugbank-id: DB00661; name: Verapamil; description: The metabolism of Almotriptan can be decreased when combined with Verapamil.; parent_key: DB00918.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Sulpiride is combined with Oxcarbazepine.; parent_key: DB00391.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Nateglinide can be increased when combined with Oxcarbazepine.; parent_key: DB00731.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The serum concentration of Levonorgestrel can be decreased when it is combined with Oxcarbazepine.; parent_key: DB00367.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Norelgestromin can be increased when combined with Oxcarbazepine.; parent_key: DB06713.", + "drugbank-id: DB00823; name: Ethynodiol diacetate; description: The therapeutic efficacy of Ethynodiol diacetate can be decreased when used in combination with Ro 12-7310.; parent_key: DB08455.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Cannabidiol is combined with Oxcarbazepine.; parent_key: DB09061.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Panobinostat can be increased when combined with Oxcarbazepine.; parent_key: DB06603.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Ruxolitinib can be increased when combined with Oxcarbazepine.; parent_key: DB08877.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with Lorcaserin.; parent_key: DB04871.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: Oxcarbazepine may increase the central nervous system depressant (CNS depressant) activities of Penthienate.; parent_key: DB13695.", + "drugbank-id: DB01418; name: Acenocoumarol; description: The serum concentration of Acenocoumarol can be increased when it is combined with Ranolazine.; parent_key: DB00243.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Norethindrone enanthate can be increased when combined with Oxcarbazepine.; parent_key: DB14678.", + "drugbank-id: DB08455; name: Ro 12-7310; description: The therapeutic efficacy of Gestodene can be decreased when used in combination with Ro 12-7310.; parent_key: DB06730.", + "drugbank-id: DB00564; name: Carbamazepine; description: The risk or severity of adverse effects can be increased when Trifluridine is combined with Carbamazepine.; parent_key: DB00432.", + "drugbank-id: DB00776; name: Oxcarbazepine; description: The metabolism of Norgestrienone can be increased when combined with Oxcarbazepine.; parent_key: DB13563." + ] + }, + { + "example_idx": 116, + "anchor_id": 18042398341168880431, + "positive_id": 4415772970401413517, + "join_paths": [ + [ + 0, + 4, + 0.474609375 + ], + [ + 0, + 12, + 0.30859375 + ], + [ + 0, + 28, + 0.2734375 + ], + [ + 0, + 29, + 0.2734375 + ], + [ + 0, + 8, + 0.2578125 + ] + ], + "rows": [ + "None: Hydromorphone is a pure opioid indicated for moderate to severe acute pain and severe chronic pain.", + "It is only prescribed when other first-line of treatments have failed, due to its high potency, abuse potential, and overdose risk.", + "Moreover, it can be prescribed off-label for refractory cough suppression." + ], + "sentences": [ + "drugbank_id: DB11691; indication: For the treatment of opioid-induced constipation [FDA Label].; pharmacodynamics: Naldemedine is an opioid receptor antagonist with restricted movement across the blood brain barrier [FDA Label]. This allows it to antagonize the periperal effects of opioid drugs such as constipation without interfering with the effects on the central nervous system.; mechanism_of_action: Naldemedine binds to and antagonizes mu-, delta-, and kappa-opioid receptors [FDA Label]. The binding of opioid agonists to peripheral mu-opioid receptors slows the transit of feces through the intestine resulting in constipation. By antagonizing mu-opioid receptors, naldemedine inhibits this effect.; toxicity: The most common adverse effects of naldemedine are abdominal pain (11%), diarrhea (7%), nausea (6%), vomiting (3%), and gastroenteritis (3%) [FDA Label].; metabolism: Naldemedine is mainly metabolized to nor-naldemedine by CYP3A [FDA Label]. Some metabolism to naldemedine-3-glucuronide occurs via UGT1A3. Both metabolites are acitive but less potent than naldemedine. The relative exposures of these metabolites are 9-13% and <3% for nor-naldemedine and naldemedine-3-glucuronide respectively. Naldemedine is also cleaved in the intestine to form benzamidine and naldemedine carboxylic acid.; absorption: Tmax is 0.75 h [FDA Label]. Administration with a high-fat meal reduces Cmax by 35% and increases Tmax to 2.5 h.; half_life: The terminal elimination half life is 11 h [FDA Label].; protein_binding: Naldemedine is 93-94% bound to human plasma proteins [FDA Label].; route_of_elimination: 57% of naldemedine is excreted in the urine with 16-18% as the parent compound and 35% is excreted in the feces [FDA Label]. ; volume_of_distribution: The apparent volume of disribution during the terminal phase is 155 L [FDA Label]; _drug_name: Naldemedine.", + "drugbank_id: DB11186; indication: Indicated as a cough suppressant to relieve cough caused by the common cold, flu, bronchitis, and sinusitis [A32160]. ; pharmacodynamics: Pentoxyverine induces an antitussive action. In animal studies, intraperitoneal administration of pentoxyverine inhibited citric-acid-induced cough in guinea-pigs _in vivo_ [A32715]. Some mice and rat studies suggest that pentoxyverine may also exert anticonvulsant activities without inducing a protective effect from NMDA-induced lethality [A32717, A32719]. Protective effects against maximal electroshock-induced seizures in a dose-related fashion was also observed following either intraperitoneal or oral administration [A32719]. In hERG-transfected cells, pentoxyverine inhibited the outward current of the hERG ion channel with half-maximal inhibition concentrations (IC50) of 3.0 µM [A32714]. In rats receiving intrathecal administration, pentoxyverine exhibited dose-dependent spinal blockade with a more sensory-selective action over motor blockade [A32720]. It induced a spinal blockade with a more sensory/nociceptive-selective action over motor blockade compared to lidocaine [A32720]. ; mechanism_of_action: While the mechanism of antitussive action of pentoxyverine is not fully understood, it is thought to be mediated via sigma-1 receptors expressed in the central nervous system [A32160]. Pentoxyverine acts as an agonist at sigma receptors with the Ki of 75±28 nM, as demonstrated in a competitive binding assay [A32715]. The function of sigma receptors on cough suppressant activities is unclear, however these receptors are highly expressed in the nucleus tractus solitarius (NTS) of the brainstem where the afferent fibres first synapse [A32715]. NTS is located very close to the cough centre in the brainstem thus may function as a ‘gate' for the cough reflex and allow sigma-1 receptor agonists to modulate afferent activity prior to reaching the cough center [A32715]. It is suggested that highly lipophilic sigma-1 agonists may penetrate the CNS following systemic administration. When administered as aerosols, sigma-1 receptor agonists may temporarily act in the periphery to modulate cough by acting activate sigma receptors expressed in the lungs [A32715]. However there is limited evidence of peripheral localization of the sigma agonists following aerosol administration and the ruling out of systemic exposure [A32715]. The local anesthesia action of pentoxyverine may occur through inhibition of voltage-gated Na(+) currents [A32720]. ; toxicity: Acute oral LD50 is 810 mg/kg in rat and 230 mg/kg in mouse [MSDS]. ; metabolism: No pharmacokinetic data available. ; absorption: In humans, maximum plasma concentrations are achieved 1.2 hours after oral dosing [A32160]. ; half_life: The half-life is 2.3 hours following oral dosing [A32160]. ; protein_binding: No pharmacokinetic data available. ; route_of_elimination: No pharmacokinetic data available. ; volume_of_distribution: No pharmacokinetic data available. ; clearance: No pharmacokinetic data available. ; _drug_name: Pentoxyverine.", + "drugbank_id: DB05724; indication: Investigated for use/treatment in pain (acute or chronic).; mechanism_of_action: ACV1 specifically blocks a subtype of a class of receptors in the peripheral nervous system called neuronal nicotinic acetylcholine receptors (nAChR).; _drug_name: alpha-Conotoxin VC 1.1.", + "drugbank_id: DB05956; indication: Investigated for use/treatment in alzheimer's disease, neurologic disorders, pain (acute or chronic), and parkinson's disease.; mechanism_of_action: EVT 101 penetrates the brain at doses that are well tolerated in man and expected to be clinically relevant, shows activity in areas relevant to pain and, importantly, modulates the activity of specific brain regions during the performance of cognitive tasks relevant to Alzheimer's disease.; _drug_name: EVT-101.", + "drugbank_id: DB01565; indication: Dihydromorphine is an opioid analgesic used for moderate to severe pain relief.; _drug_name: Dihydromorphine.", + "drugbank_id: DB04837; indication: Used in the treatment of dry cough.; pharmacodynamics: Chlophedianol (or Clofedanol) is a centrally-acting cough suppressant. It has local anesthetic and antihistamine properties, and may have anticholinergic effects at high doses.; mechanism_of_action: Suppresses the cough reflex by a direct effect on the cough center in the medulla of the brain.; metabolism: Hepatic.; _drug_name: Clofedanol.", + "drugbank_id: DB05207; indication: Central Nervous System - Neuropathic pain ; mechanism_of_action: Immune system modulator; _drug_name: SD118.", + "drugbank_id: DB05046; indication: Investigated for use/treatment in pain (acute or chronic).; mechanism_of_action: V1003 is an intranasal formulation of buprenorphine. Buprenorphine's analgesic effect is due to partial agonist activity at mu-opioid receptors. Buprenorphine is also a kappa-opioid receptor antagonist. The partial agonist activity means that opioid receptor antagonists (e.g., an antidote such as naloxone) only partially reverse the effects of buprenorphine. The binding to the mu and kappa receptors results in hyperpolarization and reduced neuronal excitability.; _drug_name: V1003.", + "drugbank_id: DB00295; indication: Morphine is used for the management of chronic, moderate to severe pain.[A176050]\n\nOpiods, including morphine, are effective for the short term management of pain. Patients taking opioids long term may need to be monitored for the development of physical dependence, addiction disorder, and drug abuse.[L5728]; pharmacodynamics: Morphine binding to opioid receptors blocks transmission of nociceptive signals, signals pain-modulating neurons in the spinal cord, and inhibits primary afferent nociceptors to the dorsal horn sensory projection cells.[A176035]\n\nMorphine has a time to onset of 6-30 minutes.[A176035] Excess consumption of morphine and other opioids can lead to changes in synaptic neuroplasticity, including changes in neuron density, changes at postsynaptic sites, and changes at dendritic terminals.[A176056]\n\nIntravenous morphine's analgesic effect is sex dependent. The EC50 in men is 76ng/mL and in women is 22ng/mL.[A176116]\n\nMorphine-6-glucuronide is 22 times less potent than morphine in eliciting pupil constriction.[A176116]; mechanism_of_action: Morphine-6-glucuronide is responsible for approximately 85% of the response observed by morphine administration.[A176059] Morphine and its metabolites act as agonists of the mu and kappa opioid receptors.[A176035] The mu-opioid receptor is integral to morphine's effects on the ventral tegmental area of the brain. Morphine's activation of the reward pathway is mediated by agonism of the delta-opioid receptor in the nucleus accumbens,[A176050] while modification of the respiratory system and addiction disorder are mediated by agonism of the mu-opioid receptor.[A176056]; toxicity: The LD50 is 0.78µg/mL in males and 0.98µg/mL in females.[A176167]\n\nPatients experiencing an overdose present with respiratory depression, somnolence, skeletal muscle flaccidity, cold and clammy skin, miosis, and mydriasis. Symptoms of overdose can progress to pulmonary edema, bradycardia, hypotension, cardiac arrest, and death.[L12108] Treat overdose with symptomatic and supportive treatment which may include the use of oxygen, vasopressors, and naloxone.[L12108]; metabolism: Morphine is 90% metabolized by glucuronidation by UGT2B7 and sulfation at positions 3 and 6.[A176059] Morphine can also be metabolized to codeine, normorphine, and morphine ethereal sulfate.[A176119]; absorption: Morphine is absorbed in the alkaline environments of the upper intestine and rectal mucosa.[A176119] The bioavailability of morphine is 80-100%.[A176164] There is significant first-pass metabolism, therefore oral doses are 6 times larger than parenteral doses to achieve the same effect. Morphine reaches steady-state concentrations after 24-48 hours.[A176035] Parenteral morphine has a Tmax of 15 minutes and oral morphine has a Tmax of 90 minutes, with a Cmax of 283nmol/L.[A176122,A176164] The AUC of morphine is 225-290nmol\\*h/L.[A176164]; half_life: Morphine has a half life of 2-3 hours.[A176116]; protein_binding: Morphine is 35% protein bound, the metabolite morphine-3-glucuronide is 10% protein bound, and morphine-6-glucuronide is 15% protein bound.[A176059]; route_of_elimination: 70-80% of an administered dose is excreted within 48 hours.[A176119] Morphine is predominantly eliminated in the urine with 2-10% of a dose recovered as the unchanged parent drug.[A176059] 7-10% of a dose of morphine is eliminated in the feces.[L12114]; volume_of_distribution: The volume of distribution of morphine is 5.31L/kg.[A176119] Morphine-6-glucuronide has a volume of distribution of 3.61L/kg.[A176119]; clearance: The apparent clearance of intravenous or subcutaneous morphine is 1600 mL/min.[A176164]; _drug_name: Morphine.", + "drugbank_id: DB08439; indication: Used for short term perioperative pain control.; metabolism: Hepatic. Metabolized primarily via CYP3A4 and 2C9 to valdecoxib and propionic acid.; half_life: 22 minutes (parecoxib); 8 hours (valdecoxib); protein_binding: 98%; _drug_name: Parecoxib.", + "drugbank_id: DB01444; indication: Dimethylthiambutene is an opioid analgesic previously used in moderate pain relief.; _drug_name: Dimethylthiambutene.", + "drugbank_id: DB05155; indication: Investigated for use/treatment in pain (acute or chronic).; mechanism_of_action: CR665 was highly selective for the peripheral kappa opioid receptor. It is intrinsically poor at penetrating the blood-brain barrier, which decreases the likelihood of CNS-mediated side effects. By acting with unprecedented selectivity at pain relieving receptors on peripheral nerves, and avoiding receptors in the central nervous system and gastrointestinal tract, CR665 has the potential to provide pain relief with minimal side effects.; _drug_name: CR665.", + "drugbank_id: DB01192; indication: For the treatment of moderate-to-severe pain.; pharmacodynamics: Oxymorphone is a semi-synthetic opioid substitute for morphine. It is a potent analgesic. Opioid analgesics exert their principal pharmacologic effects on the CNS and the gastrointestinal tract. The principal actions of therapeutic value are analgesia and sedation. Opioids produce respiratory depression by direct action on brain stem respiratory centers. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation.; mechanism_of_action: Oxymorphone interacts predominantly with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve. Also, it has been shown that oxymorphone binds to and inhibits GABA inhibitory interneurons via mu-receptors. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.; toxicity: Oxymorphone overdosage is characterized by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. Patients experiencing an overdose may develop apnea, circulatory collapse, and cardiac arrest. Intravenous mouse LD50 is 172 mg/kg.\n\n; metabolism: Oxymorphone undergoes extensive hepatic metabolism in humans. After a 10 mg oral dose, 49% was excreted over a five-day period in the urine. Of this, 82% was excreted in the first 24 hours after administration. The recovered drug-related products contained the oxymorphone (1.9%), the conjugate of oxymorphone (44.1%), the 6(beta)-carbinol produced by 6-keto reduction of oxymorphone (0.3%), and the conjugates of 6(beta)-carbinol (2.6%) and 6(alpha)-carbinol (0.1%).; half_life: 1.3 (+/-0.7) hours; route_of_elimination: Oxymorphone is highly metabolized, principally in the liver, and undergoes reduction or conjugation with glucuronic acid to form both active and inactive products. Because oxymorphone is extensively metabolized, <1% of the administered dose is excreted unchanged in the urine.; _drug_name: Oxymorphone.", + "drugbank_id: DB01558; indication: For the short-term treatment of insomnia, short-term treatment of anxiety or panic attacks, if a benzodiazepine is required, and the alleviation of the symptoms of alcohol- and opiate-withdrawal.; pharmacodynamics: Bromazepam is a lipophilic, long-acting benzodiazepine and with sedative, hypnotic, anxiolytic and skeletal muscle relaxant properties. It does not possess any antidepressant qualities. Bromazepam, like other benzodiazepines, presents a risk of abuse, misuse, and dependence. According to many psychiatric experts, Bromazepam has a greater abuse potential than other benzodiazepines because of fast resorption and rapid onset of action.; mechanism_of_action: Bromazepam binds to the GABA-A receptor producing a conformational change and potentiating its inhibitory effects. Other neurotransmitters are not influenced.; metabolism: Hepatically, via oxidative pathways (via an enzyme belonging to the Cytochrome P450 family of enzymes). One of the main metabolites is 3-hydroxybromazepam. It is pharmacologically active and the half life is similar to that of the parent compound. ; absorption: Bioavailability is 84% following oral administration. The time to peak plasma level is 1 - 4 hours. Bromazepam is generally well absorbed after oral administration. ; half_life: 10-20 hours; protein_binding: 70% ; route_of_elimination: Urine (69%), as metabolites ; volume_of_distribution: 1.56 L/kg ; clearance: 0.82 mL/min/kg. ; _drug_name: Bromazepam.", + "drugbank_id: DB09156; indication: Iopromide, as the product Iovist, is indicated for use as an X-ray contrast agent in the following procedures:\nIntra-arterial digital subtraction angiography (IA-DSA) (150 mg I/mL) \nCerebral arteriography and peripheral arteriography (300 mg I/mL) \nCoronary arteriography and left ventriculography, visceral angiography and aortography (370 mg I/mL) \nPeripheral venography (240 mg I/mL) \nExcretory urography (300 mg I/mL)\nContrast computed tomography (CT) imaging of head and body (300 mg I/mL and 370 mg I/mL) ; mechanism_of_action: Iopromide is a low osmolar, non-ionic X-ray contrast agent for intravascular administration. It functions as a contrast agent by opacifying blood vessels in the path of flow of the contrast agent, permitting radiographic visualization of the internal structures until significant hemodilution occurs.; toxicity: Most common adverse reactions (>1%) are headache, nausea, injection site and infusion site reactions, vasodilatation, vomiting, back pain, urinary urgency, chest pain, pain, dysgeusia, and abnormal vision. \nInadvertent intrathecal administration may cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema.; metabolism: Iopromide is not metabolized.; absorption: Following administration, the degree of contrast enhancement is directly related to the iodine content in the administered dose; peak iodine plasma levels occur immediately following rapid intravenous injection. Iodine plasma levels fall rapidly within 5 to 10 minutes, which can be accounted for by the dilution in the vascular and extravascular fluid compartments. Contrast enhancement appears to be greatest immediately after bolus injections (15 seconds to 120 seconds). Thus, greatest enhancement may be detected by a series of consecutive two-to-three second scans performed within 30 to 90 seconds after injection (that is, dynamic computed tomographic imaging).\nInjection may be visualized in the renal parenchyma within 30–60 seconds following rapid intravenous injection. Opacification of the calyces and pelves in patients with normal renal function becomes apparent within 1–3 minutes, with optimum contrast occurring within 5–15 minutes.\n\n; half_life: After intravenous administration to healthy young volunteers, plasma iopromide concentration time profile shows an initial distribution phase with a half-life of 0.24 hour; a main elimination phase with a half-life of 2 hours; and a terminal elimination phase with a half-life of 6.2 hours. ; protein_binding: Plasma protein binding of iopromide is 1%.; route_of_elimination: The amounts excreted unchanged in urine represent 97% of the dose in young healthy subjects. Only 2% of the dose is recovered in the feces. Similar recoveries in urine and feces are observed in middle-aged and elderly patients. This finding suggests that, compared to the renal route, biliary and/or gastrointestinal excretion is not important for iopromide. During the slower terminal phase only 3% of the dose is eliminated; 97% of the dose is disposed of during the earlier phases, the largest part of which occurs during the main elimination phase.; volume_of_distribution: 16 L; clearance: The mean total and renal clearances are 107 mL/min and 104 mL/min, respectively.; _drug_name: Iopromide.", + "drugbank_id: DB00899; indication: For use during the induction and maintenance of general anesthesia.; pharmacodynamics: Remifentanil is an opioid agonist with rapid onset and peak effect and ultra-short duration of action. The opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone. The analgesic effects of remifentanil are rapid in onset and offset. Its effects and side effects are dose dependent and similar to other opioids. Remifentanil in humans has a rapid blood-brain equilibration half-time of 1 ± 1 minutes (mean ± SD) and a rapid onset of action.; mechanism_of_action: Remifentanil is a µ-opioid agonist with rapid onset and peak effect, and short duration of action. The µ-opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone.; metabolism: By hydrolysis of the propanoic acid-methyl ester linkage by nonspecific blood and tissue esterases.; half_life: 1-20 minutes; protein_binding: 70% (bound to plasma proteins); route_of_elimination: Remifentanil is an esterase-metabolized opioid. The carboxylic acid metabolite is essentially inactive (1/4600 as potent as remifentanil in dogs) and is excreted by the kidneys with an elimination half-life of approximately 90 minutes.; volume_of_distribution: * 350 mL/kg\n* 452 ± 144 mL/kg [neonates]\n* 223 ± 30.6 mL/kg [adolescents]; clearance: * 40 mL/min/kg [young, healthy adults]; _drug_name: Remifentanil.", + "drugbank_id: DB05443; indication: Investigated for use/treatment in pain (acute or chronic) and rheumatoid arthritis. Trials are also being conducted for relieving burn pain and dermal itch.; pharmacodynamics: ADL 10-0101 is a peripheral kappa opioid agonist. It cannot cross the blood-brain barrier.; mechanism_of_action: Agonist at peripheral kappa opioid receptors; _drug_name: ADL 10-0101.", + "drugbank_id: DB06152; indication: Nylidrin is mainly indicated in conditions like arteriosclerosis, cerebrovascular disease, peripheral vascular disease, Raynaud's disease, thrombo-angitis obliterans, and thrombophlebitis [L2285]. It may sometimes be used in the treatment of peripheral vascular disorders in addition premature labor (however, the drug is not approved for premature labor)[A32531].; pharmacodynamics: \nNylidrin hydrochloride acts mainly by beta-receptor stimulation [A32529], [L2297]. Beta stimulation with nylidrin has been studied and confirmed in a variety of isolated tissues from rabbits, guinea pigs, as well as dogs. This drug has been shown to dilate arterioles in skeletal muscle and to increase cardiac output in the anesthetized dog and cat as well as the unanesthetized man. An increase in cerebral blood flow and a decrease in vascular resistance has also been reported. The result of this combination of mechanisms is an improved blood supply to ischemic tissues, with minimal change in blood pressure (generally) [L2298]. \n\n Nylidrin causes peripheral vasodilation, a positive inotropic effect, and an increased volume of gastric acid. [A32531], [L2279]. According to one study, there are two primary effects of this agent following the intra‐arterial route of administration: one, to decrease total peripheral resistance; and two, a direct effect on the heart tissue to increase cardiac output [L2297]. It also acts directly on the arteries and arterioles of the skeletal muscles. Additionally, it suppresses uterine contractility thereby preventing or halting premature labor [L2289].\n\n\n\n\n\n\n\n; mechanism_of_action: This drug is classified as a beta receptor agonist [L2284].The β2-adrenergic receptor belongs to the widely expressed _7-transmembrane receptors superfamily_, which signals through heterotrimeric _G-proteins_. They are frequently referred to as G-protein-coupled receptors because they accomplish signal transduction to the interior of the cell by interactions with _guanine nucleotide regulatory binding proteins_. The receptor-coupled G-proteins work as “molecular switches” which alternate from an inactive guanosine-diphosphate to an active guanosine-triphosphate (GTP) state, which then act to modulate all downstream cell processes. Signaling by various hormones and neurotransmitters, as well as photons and odors, follows the same general pathway, (i.e., by binding of an extracellular ligand to the receptor, which then interacts with the membrane-bound G-protein). This complex, often referred to as the ternary complex, then acts through the activated G-protein to regulate an effector, such as _adenylyl cyclase_, _phospholipase C_, or ion channels [L2296]. \n\n\nThe main effects of Nylidrin may be divided into 3 categories:\n\n**Blood vessels**\n\nVascular smooth muscle has β2-adrenoceptors that have a high binding affinity for circulating epinephrine and a lower affinity to norepinephrine released by sympathetic adrenergic nerves [L2298]. When nylidrin binds to the beta-adrenergic receptors, it prevents the binding of epinephrine, leading to decreased blood vessel contractility as epinephrine is unable to bind [L2300].\n\n**Heart:**\n\nIncreased intracellular cAMP by beta-2-agonists inhibits _myosin light chain kinase_, leading to relaxation\nThese receptors, like the receptors in the heart, are coupled to a Gs-protein, which acts stimulate the formation of cAMP. Although increased cAMP increases cardiac myocyte contraction, in vascular smooth muscle, an increase in cAMP causes smooth muscle relaxation. The reason for this is the fact that cAMP inhibits myosin light chain kinase that is responsible for phosphorylating smooth muscle myosin. Increases in intracellular cAMP caused by β2-agonists inhibit myosin light chain kinase thereby producing less contractile force (i.e., promoting relaxation) [L2298].\n\n\n**Other tissues**\n\n\nActivation of _β2-adrenoceptors_ in the lungs causes bronchodilation. β2-adrenoceptor activation leads to hepatic glycogenolysis and the pancreatic secretion of glucagon, increasing plasma glucose concentrations. β1-adrenoceptor stimulation in the kidneys promotes the release of renin, stimulating the production of angiotensin II and the subsequent release of aldosterone by the adrenal cortex [L2298].; toxicity: Adverse effects of oral sympathomimetics, such as Nylidrin, are common. The most frequent effects are hypertension, palpitations, nausea, anxiety, mydriasis, and restlessness/agitation [L2286].\n\nLarge overdoses and severe toxicity may lead to seizures, hallucinations, agitated delirium, and tachydysrhythmias including\nsupraventricular tachycardia and ventricular tachycardia. Vasospasm can lead to myocardial ischemia focal cerebrovascular deficits. Severe hypertension may also result in intracranial hemorrhage or renal insufficiency. Reflex bradycardia because of significant hypertension is possible. Prolonged agitation can lead to rhabdomyolysis and hyperthermia [L2286].\n\n; absorption: Readily absorbed from the gastrointestinal tract [L2279].; half_life: Duration of action is 10h [L2286].; _drug_name: Nylidrin.", + "drugbank_id: DB14146; indication: Loxicodegol was developed as an opioid analgesic with low abuse potential for use in treating chronic pain [L3263]. An application has been filed for FDA approval of Loxicodegol for use in treating chronic lower back pain.; pharmacodynamics: Loxicodegol displays full analgesic activity comparable to that of oxycodone, producing similar acetone-writhing test responses in mice and hot-plate test maximal latencies in rats [A34016].\n\nThe safety profile of Loxicodegol is much improved from that of other opioid analgesics [A33997]. The incidence of respiratory depression and sedation is reduced compared to oxycodone and morphine. Generalized pruritus occurred in 7.3% and 4.9% of subjects at 200mg and 400mg of Loxicodegol compared to 41.5% with 40mg oxycodone. Nausea occurred in 2.5%, 2.4%, and 7.3% with 100mg, 200mg, and 400mg of Loxecodegol compared to 29.3% with 40mg oxycodone. Lastly, vomiting occurred in 2.4% with both 200mg and 400mg Loxicodegol compared to 24.4% with 40mg oxycodone.\n\nLoxicodegol is much less addictive than other opioid analgesics. It produces a only a slight high at dosages of 400mg, peaking at scores only 25% that of oxycodone, with no difference compared to placebo at lower dosages. No differences have been noted between Loxicodegol and saline in self-administration or behavior reinforcement in monkeys or rats [A33997, A34016]; mechanism_of_action: Loxicodegol is a full agonist at the μ-opioid receptor. It also displays selectivity towards this subtype with an affinity of 237 nM compared to 4150 nM and >100000 nM for the δ- and κ-opioid receptors. The μ-opioid receptor is activated with an EC₅₀ of 12.5 μM. Activation of this receptor produces an inhibitory effect on neurotransmission through Gi/Go coupling [T1]. Opioid medications like Loxicodegol inhibit voltage gated Ca²⁺ channel opening presynaptically on C fibres and activate inward-rectifying K⁺ channels post-synaptically on 2nd order neurons, leading to hyperpolarization. Together, these prevent the nociceptive signal from traveling up the spinal cord to the brain. In the brain, opioids work through a mechanism of inhibition of inhibition to allow regulatory neurons to suppress nociception. ; absorption: Loxicodegol has a Tmax of 1.8h and a bioavailability of 34% with oral administration [A34016]. It enters the brain about 17-70 times more slowly than oxycodone [A33997]. Loxicodegol is also a p-glycoprotein substrate further reducing its transport into the brain.; half_life: Loxicodegol has a half-life of 4.53 h allowing for a longer duration of action [A34016].; volume_of_distribution: Loxicodegol has a steady-state Vd of 4.19 L/kg [A34016].; clearance: Loxicodegol has a clearance rate of 59.3 mL/min/kg [A34016].; _drug_name: Loxicodegol.", + "drugbank_id: DB06738; indication: For the treatment of all types of severe pain, such as postoperative, cancer, kidney stones and fractures.; mechanism_of_action: Ketobemidone (Cliradon, Ketogan, Ketodur, Cymidon, Ketorax, &c.) is a powerful opioid analgesic. It also has some NMDA-antagonist properties. This makes it useful for some types of pain that don't respond well to other opioids. The most commonly cited equalisation ratio for analgesic doses is 25 mg of ketobemidone hydrobromide to 60 mg of morphine hydrochloride or sulfate and circa 8 mg of ketobemidone by injection.; toxicity: Base: Rat Intravenous LD50: 10 mg/kg; Mouse Intravenous LD50: 14 mg/kg.\nHydrochloride salt: Rat Oral LD50: 215 mg/kg; Rat Intravenous LD50: 40 mg/kg\n; metabolism: Ketobemidone is mainly metabolised by conjugation of the phenolic hydroxyl group, and by N-desmethylation. Only about 13-24% is excreted unchanged after iv. administration.; absorption: 34% (oral), 44% (rectal); half_life: Plasma half-life: 2.42 +/- 0.41 h (m +/- SD).\nElimination half-life: 3.27 +/- 0.32 h; _drug_name: Ketobemidone.", + "drugbank_id: DB09272; indication: For the treatment of irritable bowel syndrome with diarrhea (IBS-D).; mechanism_of_action: Eluxadoline is a mu-opioid receptor agonis, kappa opioid receptor agonist and a delta opioid receptor antagonist. Eluxadoline is used for diarrhea predominant IBS because it reduces intestinal contractility and normalizes stress-induced acceleration of upper GI transit. Antagonistic activity at the delta receptor minimizes the constipating effect usually seen by mu-opioid receptor agonists alone. Because of it's limited systemic bioavailability, there may be less side effects associated with the use of eluxadoline in comparison with other therapies used to treat diarrhea predominant IBS. ; toxicity: The most common adverse reactions (>5%) are constipation, nausea and abdominal pain. ; metabolism: The metabolism of eluxadoline is currently unclear, however evidence suggests limited glucoronidation forms an acyl glucuronide metabolite that is then excreted into urine. ; absorption: The oral absorption of eluxadoline is poor - estimated to be 1.02%, this could be attributed to poor in vitro GI permeability, and its zwitterionic nature leading to a negatively charged molecule across the GI pH range.; half_life: The mean plasma elimination half-life ranged from 3.7 hours to 6 hours. ; protein_binding: 81% ; route_of_elimination: 82% excreted in feces, <1% excreted in urine.; _drug_name: Eluxadoline.", + "drugbank_id: DB05236; indication: For the treatment of stroke.; pharmacodynamics: ReN001 is a clonal human neural stem cell line which has been conditionally immortalized using the fusion transgene c-mycERTAM to allow controlled expansion when cultured in the presence of 4-hydroxytamoxifen. The cell line has been banked and fully characterized to assure there is genetic stability and no phenotypic drift with extended passages. In vivo studies determined the ability of the cell line to survive after implantation into damaged brain and its efficacy in the reduction of chronic behavioural dysfunction after implantation into a rodent model of stroke damage. A further study was conducted in this model and a dose-dependent effect was observed on behavioural recovery. No safety or toxicology issues were identified in in vivo studies with this cell line.; _drug_name: ReN001.", + "drugbank_id: DB00726; indication: For the treatment of depression and depression accompanied by anxiety, agitation or sleep disturbance; pharmacodynamics: Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic.; mechanism_of_action: Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).; toxicity: Side effects include agitation, coma, confusion, convulsions, dilated pupils, disturbed concentration, drowsiness, hallucinations, high fever, irregular heart rate, low body temperature, muscle rigidity, overactive reflexes, severely low blood pressure, stupor, vomiting; metabolism: Hepatic; absorption: Rapid absorption; half_life: 11-18 hrs; protein_binding: 93%-96% (to plasma proteins); _drug_name: Trimipramine.", + "drugbank_id: DB00651; indication: For relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema.; pharmacodynamics: Dyphylline, a xanthine derivative, is a bronchodilator used for relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema. Dyphylline is a xanthine derivative with pharmacologic actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to a lesser degree.; mechanism_of_action: The bronchodilatory action of dyphylline, as with other xanthines, is thought to be mediated through competitive inhibition of phosphodiesterase with a resulting increase in cyclic AMP producing relaxation of bronchial smooth muscle as well as antagonism of adenosine receptors.; toxicity: LD50=1954 mg/kg (orally in mice); metabolism: Hepatic; half_life: 2 hours (range 1.8 - 2.1 hours); protein_binding: 84%; route_of_elimination: Dyphylline exerts its bronchodilatory effects directly and, unlike the­ophylline, is excreted unchanged by the kidneys without being metabolized by the liver. Approximately 88% of a single oral dose can be recovered from the urine unchanged.; _drug_name: Dyphylline.", + "drugbank_id: DB05346; indication: Investigated for use/treatment in osteoarthritis and pain (acute or chronic).; mechanism_of_action: An active ingredients in WL-1002 is civamide which has anticeptic property.The antinociception of civamide is probably mediated two mechanisms: (i) an acute receptor occupancy dependent effect; and (ii) a persistent and receptor independent effect which is initiated by the acute exposure to the drug.; _drug_name: WL-1002.", + "drugbank_id: DB11362; indication: Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce risk of hospitalization.; pharmacodynamics: At the maximum tolerated dose of 1600 mcg twice per day, selexipag was not found to prolong the QT interval to a clinically relevant extent. Both selexipag and its metabolite caused concentration-dependent inhibition of platelet aggregation in vitro with IC50 of 5.5 µM and 0.21 µM, respectively. However, at clinically relevant concentrations, there was no effect on platelet aggregation test parameters following multiple dose administration of selexipag in healthy patients. ; mechanism_of_action: Selexipag is a selective prostacyclin (IP, also called PGI2) receptor agonist. The key features of pulmonary arterial hypertension include a decrease in prostacyclin and prostacyclin synthase (enzyme that helps produce prostacyclin) in the lung. Prostacyclin is a potent vasodilator with anti-proliferative, anti-inflammatory, and anti-thrombotic effects; therefore, there is strong rationale for treatment with IP receptor agonists. Selexipag is chemically distinct as it is not PGI2 or a PGI2 analogue and has high selectivity for the IP receptor. It is metabolized by carboxylesterase 1 to yield an active metabolite (ACT-333679) that is approximately 37 times more potent than selexipag. Both selexipag and its metabolite are selective for the IP receptor over other prostanoid receptors. ; toxicity: A 40-70% increase in exposure was observed in subjects with severe renal impairment. \n; metabolism: Selexipag yields its active metabolite by hydrolysis of the acylsulfonamide by the enzyme hepatic carboxylesterase 1. Oxidative metabolism catalyzed by CYP3A4 and CYP2C8 results in hydroxylated and dealkylated products. UGT1A3 and UGT2B7 are involved in the glucuronidation of the active metabolite. Other than active metabolite, other metabolites in circulation do not exceed 3% of the total drug-related material. ; absorption: After oral administration, maximum concentrations of selexipag and its metabolite were observed to be reached at 1-3 and 3-4 hours, respectively. Absorption was impaired in the presence of food, resulting in delayed time to maximum concentration as well as ~30% lower peak plasma concentration. However, exposure was not found to be significantly affected by food.; half_life: Selexipag's terminal half life is 0.8-2.5 hours. The active metabolite's terminal half life is 6.2-13.5 hours. ; protein_binding: Both selexipag and its active metabolite are highly protein bound, approximately 99%.; route_of_elimination: 93% in feces, 12% in urine. ; clearance: On average, 35 L/hour.; _drug_name: Selexipag.", + "drugbank_id: DB04828; indication: Zomepirac was indicated for the management of mild to severe pain.; _drug_name: Zomepirac.", + "drugbank_id: DB09017; indication: Brotizolam is indicated for 2-4 weeks in the treatment of severe or debilitating insomnia. ; metabolism: There are two primary metabolites: 1-methyl-hydroxy- and the 4-hydroxy-derivatives (Eberts et al., 1981; Boehringer Ingelheim, product information). The 4-hydroxymetabolites have a pharmacological activity which is far less than that of the parent drugs, but the 1-methyl-hydroxymetabolites probably have comparable activity (Gall et al., 1978; Jochemsen et al., 1982; Sethy & Harris, 1982; Jochemsen et al., unpublished results). These active compounds are, however, not present in plasma in measurable amounts following a single dose of brotizolam to young healthy subjects (Jochemsen et al., 1982; Jochemsen et al., unpublished results).; absorption: The plasma concentration profile of brotizolam can be described as a one compartmental open model with first-order absorption.; half_life: 4.4 hours.; protein_binding: The mean value of the free fraction (%): 8.4 ± 0.7.; volume_of_distribution: 0.63 l/kg.; clearance: Total clearance: 109 ml/min.; _drug_name: Brotizolam.", + "drugbank_id: DB00854; indication: For the management of moderate to severe pain or as a preoperative medication where an opioid analgesic is appropriate.; pharmacodynamics: Levorphanol is a potent synthetic opioid analgesic indicated for the management of moderate to severe pain or as a preoperative medication where an opioid analgesic is appropriate. Levorphanol is similar to morphine in its actions, however it is up to 8 times more potent than morphine. Levorphanol produces a degree of respiratory depression similar to that produced by morphine at equianalgesic doses, and like many mu-opioid drugs, levorphanol produces euphoria or has a positive effect on mood in many individuals.; mechanism_of_action: Like other mu-agonist opioids it is believed to act at receptors in the periventricular and periaqueductal gray matter in both the brain and spinal cord to alter the transmission and perception of pain.; toxicity: LD50=150 mg/kg (orally in rats). Signs of overdose include nausea, emesis, dizziness, respiratory depression, hypotension, urinary retention, cardiac arrhythmias, allergic reactions, skin rash, and uticaria.; metabolism: Levorphanol is extensively metabolized in the liver and is eliminated as the glucuronide metabolite.; absorption: Levorphanol is well absorbed after PO administration with peak plasma concentrations occurring approximately 1 hour after dosing.; half_life: 11-16 hours; protein_binding: 40%; volume_of_distribution: * 10 to 13 L/kg; clearance: * 0.78 to 1.1 L/kg/hr; _drug_name: Levorphanol.", + "drugbank_id: DB11490; indication: Used to reverse opioid overdose.; _drug_name: Nalorphine.", + "drugbank_id: DB05773; indication: Used in HER2-positive, metastatic breast cancer patients who have already used taxane and/or trastuzumab for metastatic disease or had their cancer recur within 6 months of adjuvant treatment.\n\n; pharmacodynamics: Trastuzumab emtansine was evaluated in two Herceptin-responsive and one Herceptin-resistant breast tumor models. In the Herceptin-responsive models, Trastuzumab-DM1 caused complete tumor regression in all mice, whereas Herceptin alone slowed tumor growth. In the Herceptin- resistant model, Herceptin alone had no effect on tumor growth. In contrast, Trastuzumab-DM1 caused >90% tumor reduction in all mice. In this Herceptin- resistant model, tumor regrowth was observed after cessation of Trastuzumab- DM1 treatment, yet regression re-occurred when dosing was resumed. The effect was specific for HER2-positive tumors. Thus the physiological effects of trastuzumab emtansine are cell cycle arrest and cell death by apoptosis. ; mechanism_of_action: Trastuzumab emtansine is a HER2 antibody drug conjugate. The antibody portion is trastuzumab, which is humanized anti-HER2 IgG1, and produced in the mammalian Chinese Hamster Ovary cells. The drug portion is DM1, which is a maytansine derivative that inhibits microtubules. These two portions are covalently connected by 4-[N-maleimidomethyl] cyclohexane-1-carboxylate (MCC), which is a stable thioether linker. Together MCC and DM1 are called emtansine and are produced by chemical synthesis.\nTrastuzumab emtansine binds to the HER2 receptor’s sub-domain IV and goes into the cell by receptor-mediated endocytosis. Lysosomes degrade trastuzumab emtansine and release DM1. DM1 binds to tubulin in microtubules and inhibits microtubule function producing cell arrest and apoptosis. As well, similar to trastuzumab, in vitro studies have shown that both HER2 receptor signalling inhibition and antibody-dependent cytotoxicity are mediated by trastuzumab emtansine.\n\n; toxicity: The FDA label includes a black box warning of serious side effects such as hepatotoxicity, embryo-fetal toxicity, and cardiac toxicity. ; metabolism: Trastuzumab emtansine undergoes lysosomal degradation to MCC-DM1, Lys-MCC-DM1, and DM1. All of these products are detected at low levels in the plasma. DM1 undergoes further degradation by CYP3A4 and CYP3A5, but DM1 does not induce or inhibit any of the CYP450 enzymes.\n ; absorption: The absorption/ bioavailability should be close to 100% since trastuzumab emtansine is administered IV.; half_life: Trastuzumab emtansine has a long half life of about 4 days.; protein_binding: DM1 has a plasma protein binding value of 93%.; route_of_elimination: The route of elimination has not yet been fully elucidated.; volume_of_distribution: The volume of distribution of trastuzumab emtansine is about 3.13 L.; clearance: After IV infusion, trastuzumab emtansine has a clearance of 0.68 L/day.; _drug_name: Trastuzumab emtansine.", + "drugbank_id: DB01439; mechanism_of_action: 3-Methylthiofentanyl binds to the mu, delta, and kappa opioid receptors. These ultimately lead to decreased pain sensation as well as a number of side effects, such as euphoria, sedation, depressed breathing.; toxicity: Opioid analgesics are associated with itching, nausea, and potentially serious respiratory depression, which can be life-threatening.; _drug_name: 3-Methylthiofentanyl.", + "drugbank_id: DB09543; indication: Ointments or liniments containing methyl salicylate are applied topically as counter irritant for relief of acute pain associated with lumbago,sciatica and rheumatic conditions. Local analgesics for human and veterinary medicine.; pharmacodynamics: Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow. It is pharmacologically similar to aspirin and other NSAIDs but as a topical agent it primarily acts as a rubefacient and skin irritant. Counter-irritation is believed to cause a soothing sensation of warmth.; mechanism_of_action: Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves [A19285]. This is thought to mask the underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where it reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2. ; toxicity: Oral LD50 values (mg/kg) for mouse, rat and rabbit are 1110, 887 and 1300, respectively. Oral LD50 values for child and adult human (mg/kg) are 228 and 506, respectively. Although systemic toxicity from topical administration is rare, methyl salicylate can be absorbed in intract skin to cause stimulation of the central nervous system respiratory center, disturbance of lipid and carbohydrate metabolism, and disturbance of intracellular respiration. Severe toxicity can result in acute lung injury, lethargy, coma, seizures, cerebral edema, and death. In case of salicylate poisoning, the treatment consists of general supportive care, gastrointestinal decontamination with activated charcoal in cases of salicylate ingestion, and monitoring of serum salicylate concentrations. Bicarbonate infusions or hemodialysis can be used to achieve enhanced salicylate elimination [A19287].; metabolism: Minor metabolism may occur in various tissues but hepatic metabolism constitutes the majority of metabolic processes of absorbed methyl salicylate. It is mainly hydrolyzed to salicylic acid via hepatic esterase enzymes. Conjugation with glycine forms salicyluric acid and conjugation with glucuronic forms ester or acyl and ether or phenolic glucuronide, which are the three main metabolites. ; absorption: Approximately 12-20% of topically applied methyl salicylate may be systemically absorbed through intact skin within 10 hours of application, and absorption varies with different conditions such as surface area and pH. Dermal bioavailability is in the range of 11.8 – 30.7%. For the assessment of potential oral exposure to salicylates, bioavailability is assumed to be 100% [L777].; half_life: The plasma half-life for salicylate is 2 to 3 hr in low doses and about 12 hr at usual anti-inflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication. ; protein_binding: Degree of albumin binding depends on the plasma concentration of the compound; route_of_elimination: Excreted by kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronide (5%), and gentisic acid (less than 1%).; volume_of_distribution: After absorption, methyl salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes. Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus. The drug readily crosses the placental barrier. ; _drug_name: Methyl salicylate.", + "drugbank_id: DB05232; indication: For the treatment of chronic and breakthrough pain in advanced cancer patients as well as for the treatment of opioid dependence.; mechanism_of_action: Tetrodotoxin binds to site 1 of the fast voltage-gated sodium channel located at the extracellular pore opening. The binding of any molecules to this site will temporarily disable the function of the ion channel. Saxitoxin and several of the conotoxins also bind the same site.; toxicity: Death has occurred within 17 minutes of ingestion.; _drug_name: Tetrodotoxin.", + "drugbank_id: DB01242; indication: May be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette’s disorder).\nUnlabeled indications include: depression, panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy (limited evidence), autistic disorder (limited evidence), trichotillomania (limited evidence), onchophagia (limited evidence), stuttering (limited evidence), premature ejaculation, and premenstrual syndrome. ; pharmacodynamics: Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α1 and β1 receptors are sensitized, α2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.; mechanism_of_action: Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α1-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.; toxicity: Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with Anafranil either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg.\nSide effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. \nWithdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia. ; metabolism: Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by N-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine N-oxide formed by N-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and N-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical contribution remains unknown.; absorption: Well absorbed from the GI tract following oral administration. Bioavailability is approximately 50% orally due to extensive first-pass metabolism. Bioavailability is not affected by food. Peak plasma concentrations occurred 2-6 hours following oral administration of a single 50 mg dose. The peak plasma concentration ranged from 56 ng/mL to 154 mg/mL (mean, 92 ng/mL). There are large interindividual variations in plasma concentrations occur, partly due to genetic differences in clomipramine metabolism. On average, steady state plasma concentrations are achieved in 1-2 weeks following multiple dose oral administration. Smoking appears to lower the steady-state plasma concentration of clomipramine, but not its active metabolite desmethylclomipramine. ; half_life: Following oral administration of a single 150 mg dose of clomipramine, the average elimination half-life of clomipramine was 32 hours (range: 19-37 hours) and of desmethylclomipramine was 69 hours (range: 54-77 hours). Elimination half-life may vary substantially with different doses due to saturable kinetics (i.e. metabolism). ; protein_binding: Clomipramine is approximately 97-98% bound to plasma proteins, principally to albumin and possibly to α1-acid glycoprotein. Desmethylclomipramine is 97-99% bound to plasma proteins. ; route_of_elimination: Urine (51-60%) and feces via biliary elimination (24-32%); volume_of_distribution: ~ 17 L/kg (range: 9-25 L/kg).\nClomipramine is capable of distributing into the cerebrospinal fluid, the brain, and into breast milk. ; _drug_name: Clomipramine.", + "drugbank_id: DB09217; indication: Used for the treatment of pain inflammation and fever in horses and dogs.; _drug_name: Firocoxib.", + "drugbank_id: DB06204; indication: The immediate-release formulation of tapentadol is indicated for the relief of moderate to severe acute pain. The long-acting formulation serves as a continuous, around-the-clock analgesic that is indicated for the relief of moderate to severe chronic pain or neuropathic pain associated with diabetic peripheral neuropathy. ; pharmacodynamics: Tapentadol is a centrally-acting synthetic analgesic that is 18 times less potent than morphine in binding mu-opioid receptors. It also increases norepinephrine concentrations in the brains of rats via inhibition of norepinephrine reuptake. Selective mu-opioid antagonists like naloxone can block analgesia from tapentadol. It also has not effect on the QT interval. ; mechanism_of_action: Tapendadol causes large increases in levels of extracellular norepinephrine (NE) due to a dual mechanism of action involving mu opioid receptor (MOR) agonism as well as noradrenaline reuptake inhibition.\n\n; toxicity: Oral, rabbit: LD50 = 3200 mg/kg;\nOral, mouse: LD50 = 300 mg/kg;\nOral, rat: LD50: 980 mg/kg;\nThe most common reasons for discontinuation due to adverse events were dizziness, nausea, vomiting, somnolence, and headache. ; metabolism: 97% of the dose is metabolized mostly via conjugation with glucuronic acid to produce glucuronides. Tapentadol is also metabolized into N-desmethyl tapentadol (13%) by CYP2C9 and CYP 2C19. CYP2D6 is involved in the formation of the metabolite, hydroxy tapentadol (2%). All metabolites are inactive. ; absorption: Bioavailability, immediate release (IR), 86 mg: 32%; \nBioavailability, extended release (ER), 86 mg: 32%; \nCmax, IR: 64.2 ng/mL;\nCmax, ER: 22.5 ng/mL; \nT max, IR: 1.5 hours;\nT max, ER: 5.0 hours;\nTapentadol accumulates following multiple repeat doses. \n\n; half_life: Elimination half-life, IV: 4 hours. ; protein_binding: ~20% ; route_of_elimination: Tapentadol and its metabolites are excreted almost exclusively (99%) via the kidneys. Approximately 70% (55% O-glucuronide and 15% sulfate of tapentadol) is excreted in conjugated form. A total of 3% of drug was excreted in urine as unchanged drug. ; volume_of_distribution: Following IV administration, volume of distribution is 540 ± 98 L. ; clearance: Total clearance = 1530 ± 177 ml/min. ; _drug_name: Tapentadol.", + "drugbank_id: DB01645; indication: Currently Genistein is being studied in clinical trials as a treatment for prostate cancer. ; mechanism_of_action: Genistein may inhibit cancer cell growth by blocking enzymes required for cell growth. \n\nGenistein may decrease cardiovascular risk in postmenopausal women by interacting with the nuclear estrogen receptors to alter the transcription of cell specific genes. In randomized clinical trials, genistein was seen to increase the ratio of nitric oxide to endothelin and improved flow-mediated endothelium dependent vasodilation in healthy postmenopausal women [A14417]. In addition, genistein may have beneficial effects on glucose metabolism by inhibiting islet tyrosine kinase activity as well as insulin release dependent on glucose and sulfonylurea [A14417]. ; _drug_name: Genistein.", + "drugbank_id: DB00469; indication: For the treatment of rheumatoid arthritis, osteoarthritis, backache, and pain.; pharmacodynamics: Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.; mechanism_of_action: The antiinflammatory effects of tenoxicam may result from the inhibition of the enzyme cycooxygenase and the subsequent peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, their inhibition accounts for the peripheral analgesic effects of tenoxicam. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.; metabolism: Tenoxicam is metabolized in the liver to several pharmacologically inactive metabolites (mainly 5'-hydroxy-tenoxicam).; absorption: Oral absorption of tenoxicam is rapid and complete (absolute bioavailability 100%).; half_life: 72 hours (range 59 to 74 hours); protein_binding: 99%; _drug_name: Tenoxicam.", + "drugbank_id: DB01209; indication: Indicated in the treatment of moderate to severe pain.; pharmacodynamics: Dezocine is a parenteral narcotic analgesic possessing both agonist and antagonist activity. It is similar to morphine with respect to analgesic potency and onset and duration of action. The narcotic antagonist activity is greater than that of pentazocine.; mechanism_of_action: Dezocine is a opioid analgesic drug of mixed agonist-antagonist type. It binds with stereospecific receptors at many sites within the central nervous system (CNS) to alter processes affecting both the perception of pain and the emotional response to pain. At least 2 of these types of receptors (mu and kappa) mediate analgesia. Mu receptors are widely distributed throughout the CNS, especially in the limbic system (frontal cortex, temporal cortex, amygdala, and hippocampus), thalamus, striatum, hypothalamus, and midbrain as well as laminae I, II, IV, and V of the dorsal horn in the spinal cord. Kappa receptors are localized primarily in the spinal cord and in the cerebral cortex.; toxicity: Symptoms of overdose include cold and clammy skin, confusion, nervousness, or severe restlessness, convulsions (seizures), severe dizziness, severe drowsiness, low blood pressure, pinpoint pupils of eyes, slow heartbeat, slow or troubled breathing and severe weakness.; metabolism: Hepatic, via conjugation (glucuronidation).; absorption: Rapid and complete following intramuscular administration.; half_life: Elimination half-life following intramuscular administration averages 2.2 hours. Elimination half-life following a 5mg intravenous dose averages 1.7 to 2.6 hours (range 0.6 to 4.4 hours) while a 10mg dose averages 2.4 to 2.6 hours (range 1.2 to 7.4 hours). In patients with hepatic cirrhosis, the half-life is increased by 30 to 50%.; _drug_name: Dezocine.", + "drugbank_id: DB01050; indication: Ibuprofen is the most commonly used and prescribed NSAID. It is very common over the counter medication widely used as an analgesic, anti-inflammatory and antipyretic.[A39096]\n\nThe use of ibuprofen and its enantiomer [DB09213] in a racemic mix is common for the management of mild to moderate pain related to dysmenorrhea, headache, migraine, postoperative dental pain, spondylitis, osteoarthritis, rheumatoid arthritis, and soft tissue disorder.[A39097]\n\nDue to its activity against prostaglandin and thromboxane synthesis, ibuprofen has been attributed to alteration of platelet function and prolongation of gestation and labor.[A39092]\n\nAs ibuprofen is a widely used medication, the main therapeutic indications are:\n\n* Patent Ductus Arteriosus - it is a neonatal condition wherein the ductus arteriosus (blood vessel that connects the main pulmonary artery to the proximal descending aorta) fails to close after birth causing severe risk of heart failure. The prostaglandin inhibition of ibuprofen has been studied for the treatment of this condition as it is known that prostaglandin E2 is responsible for keeping the ductus arteriosus open.[A39100]\n\n* Rheumatoid- and osteo-arthritis - ibuprofen is very commonly used in the symptomatic treatment of inflammatory, musculoskeletal and rheumatic disorders.[A39176]\n\n* Cystic fibrosis - the use of high dosages of ibuprofen has been proven to decrease inflammation and decreasing polymorphonuclear cell influx in the lungs.[A39177]\n\n* Orthostatic hypotension - ibuprofen can induce sodium retention and antagonize the effect of diuretics which has been reported to be beneficial for patients with severe orthostatic hypotension.[A1651]\n\n* Dental pain - ibuprofen is used to manage acute and chronic orofacial pain.[A10901]\n\n* Minor pain - ibuprofen is widely used to reduce minor aches and pains as well as to reduce fever and manage dysmenorrhea. It is very commonly used for the relief of acute indications such as fever and tension headaches.[A39092]\n\n* Investigational uses - efforts have been put into developing ibuprofen for the prophylaxis of Alzheimer's disease, Parkinson disease, and breast cancer.[A39092]; pharmacodynamics: Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials.[A39190]\n\nThe antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region.[A39190]\n\nThe use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen.[A39190]\n\nThe administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms.[A39092] \n\nIbuprofen is largely used in OTC products such as an agent for the management of dysmenorrhea which has been proven to reduce the amount of menstrual prostanoids and to produce a reduction in the uterine hypercontractility.[A39181] As well, it has been reported to reduce significantly the fever and the pain caused by migraines.[A39182, A39183] This effect is thought to be related to the effect on platelet activation and thromboxane A2 production which produces local vascular effects in the affected regions. This effect is viable as ibuprofen can enter in the central nervous system.[A39190]\n\nIn the investigational uses of ibuprofen, it has been reported to reduce neurodegeneration when given in low doses over a long time.[A39184] On the other hand, its use in Parkinson disease is related to the importance of inflammation and oxidative stress in the pathology of this condition.[A39185] The use of ibuprofen for breast cancer is related to a study that shows a decrease of 50% in the rate of breast cancer.[A39186]; mechanism_of_action: The exact mechanism of action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway.[L4614]\n\nIbuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration.[A39195]; toxicity: The symptoms of overdose are presented in individuals that consumed more than 99 mg/kg. Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients).[A39200]\n\nThe reported LD50 of ibuprofen is of 636 mg/kg in rat, 740 mg/kg in mouse and 495 mg/kg in guinea pig.[MSDS]; metabolism: Ibuprofen is rapidly metabolized and biotransformed in the liver to the formation of major metabolites which are the hydroxylated and carboxylated derivatives.[A39092] As soon as it is absorbed, the R-enantiomer undergoes extensive enantiomeric conversion (53-65%) to the more active S-enantiomer _in vivo_ by the activity of alpha-methylacyl-CoA racemase.[A39194] \n\nIbuprofen metabolism can be divided in phase I which is represented by the hydroxylation of the isobutyl chains for the formation of 2 or 3-hydroxy derivatives followed by oxidation to 2-carboxy-ibuprofen and p-carboxy-2-propionate. These oxidative reactions are performed by the activity of the cytochrome P450 isoforms CYP 2C9, CYP 2C19 and CYP 2C8. Therefore, these enzymes participate in the oxidation of the alkyl side chain to hydroxyl and carboxyl derivatives. From this enzymes, the major catalyst in the formation of oxidative metabolites is the isoform CYP 2C9.[A39190]\n\nThe metabolic phase I is followed by a phase II in which the oxidative metabolites may be conjugated to glucuronide prior to excretion. This activity forms phenolic and acyl glucuronides.[A39190]; absorption: It is very well absorbed orally and the peak serum concentration can be attained in 1 to 2 hours after extravascular administration. When ibuprofen is administered immediately after a meal there is a slight reduction in the absorption rate but there is no change in the extent of the absorption.[A39092] \n\nWhen orally administered, the absorption of ibuprofen in adults is very rapidly done in the upper GI tract.[A39190] The average Cmax, Tmax and AUC ranges around 20 mcg/ml, 2 h and 70 mcg.h/ml. These parameters can vary depending on the enantiomer form, route, and dose of administration.[A39190]; half_life: The serum half-life of ibuprofen is 1.2-2 hours.[A39092] In patients with a compromised liver function, the half-life can be prolonged to 3.1-3.4 hours.[A39190]; protein_binding: Ibuprofen dosage is more than 99% bound to plasma proteins and site II of purified albumin, binding appears to be saturable and becomes non-linear at concentrations exceeding 20 mcg/ml.[A39092]; route_of_elimination: Ibuprofen is rapidly metabolized and eliminated in the urine thus, this via accounts for more than 90% of the administered dose. It is completely eliminated in 24 hours after the last dose and almost all the administered dose goes through metabolism, representing about 99% of the eliminated dose.[A39092] The biliary excretion of unchanged drug and active phase II metabolites represents 1% of the administered dose.[A39190]\n\nIn summary, ibuprofen is excreted as metabolites or their conjugates. The elimination of ibuprofen is not impaired by old age or the presence of renal impairment.[A39092] ; volume_of_distribution: The apparent volume of distribution of ibuprofen is of 0.1 L/kg.[A39195]; clearance: The clearance rate ranges between 3-13 L/h depending on the route of administration, enantiomer type and dosage.[A39190]; _drug_name: Ibuprofen.", + "drugbank_id: DB05432; indication: Investigated for use/treatment in addictions, dementia, parkinson's disease, schizophrenia and schizoaffective disorders, and strokes.; mechanism_of_action: DAS-431 IV is a dopamine D1 receptor agonist which is in Phase II evaluation for the treatment of cognitive impairment in the elderly and cocaine addiction and is in development for a broad range of CNS diseases, including schizophrenia. Dopamine D1 receptors are thought to play a role in mediating cognitive processes in the prefrontal cortex, particularly working memory. The number of D1 receptors appears to be decreased in the elderly, chronic addicts, patients with schizophrenia and, possibly, patients with Parkinson's disease and those who have experienced a stroke. DAS-431 directly activates D1 receptors in the prefrontal cortex and may be useful in treating these conditions. ; _drug_name: DAS-431 IV.", + "drugbank_id: DB09214; indication: For short-term treatment of mild to moderate pain, including dysmenorrhoea, musculoskeletal pain and toothache [L1302]. ; pharmacodynamics: This drug is an isomer of ketoprofen. Dexketoprofen a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic properties [L1299]. ; mechanism_of_action: It is a non-steroidal anti-inflammatory drug (NSAID) that reduces prostaglandin synthesis via inhibition of cyclooxygenase pathway (both COX-1 and COX-2) activity [L1299].; toxicity: Nausea and/or vomiting, stomach pain, diarrhea, digestive problems (dyspepsia) are the most common symptoms of toxicity. More toxicity symptoms include dizziness, sleepiness, disturbed sleep, nervousness, headache, palpitations, flushing, stomach problems, constipation, dry mouth, flatulence, skin rash, tiredness, pain, feeling feverish and shivering, and malaise.\n\nSevere toxicity can lead to thrombocytopenia and anemia with bleeding episodes. Dexketoprofen is associated with a small increased risk of myocardial infarction [L1302].\n; metabolism: Dexketoprofen is highly lipophilic, and is metabolized in the liver by glucuronidation [L1304]. In one study, after oral administration of 25 mg of dexketoprofen to young healthy adults, Tmax was approximately 30 min for a Cmax of 3.7 ± 0.72 mg/l [L1305]. Dexketoprofen trometamol is metabolized by the hepatic cytochrome P450 enzymes (CYP2C8 and CYP2C9) [L1305]. \n\nDexketoprofen trometamol has a number of metabolites, with hydroxyl derivatives making up the greatest volume [L1305]. In humans, hydroxylation plays a minor role. \n\nDexketoprofen is primarily conjugated to an acyl-glucuronide [L1305]; absorption: After oral ingestion, the Dexketoprofen onset of action is within 30 minutes. The plasma half-life of Dexketoprofen is about 4-6 hours. The Cmax is about 30 minutes [L1204]; half_life: 1.65 h [L1299]; protein_binding: Highly protein bound [L1299].; route_of_elimination: Approximately 70 to 80% of the ingested dose is recovered in the urine during the first 12 hours post-ingestion, mainly as the acyl-conjugated form of the drug [L1301].; volume_of_distribution: <0.25 L/kg [L1299] ; clearance: Mainly cleared via glucuronide conjugation and followed by renal excretion, mainly unchanged [L1299].\n; _drug_name: Dexketoprofen.", + "drugbank_id: DB05364; indication: Investigated for use/treatment in pain (acute or chronic).; mechanism_of_action: ROX-888 is a intranasal formulation of the broadly used injectible analgesic, ketorolac. It has ability to provide effective analgesia in acute medical conditions resulting in moderate-severe pain, without the disabling side effects of opioid analgesics; _drug_name: ROX-888.", + "drugbank_id: DB01708; indication: DHEA is taken as a supplement for a variety of unsubstantiated indications. The following indications have shown promise and are backed up by some scientific evidence: schizophrenia (DHEA may be more effective in women than men); improving the appearance of older people’s skin (taking DHEA by mouth seems to increase skin thickness and moisture, and decrease facial “age spots” in elderly men and women); improving ability to achieve an erection in men with sexual dysfunction. Additionally, DHEA has shown promise in improving symptoms of lupus (SLE). Taking DHEA by mouth along with conventional treatment may help reduce the number of times symptoms flare up and may allow a reduction in the dose of prescription drugs needed. DHEA may also help SLE symptoms such as muscle ache and mouth ulcers. DHEA also seems to strengthen bones in SLE patients being treated with high-dose steroids (corticosteroids).\nDHEA also shows promise in the treatment of osteoporosis. Taking DHEA by mouth daily seems to improve bone mineral density (BMD) in older women and men with osteoporosis or osteopenia (pre-osteoporosis). DHEA may also increase BMD in young women with the eating disorder called anorexia nervosa. DHEA is often prescribed in India for the induction of ovulation to improve chances of pregnancy.; pharmacodynamics: DHEA is naturally produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. DHEA is increased by exercise and calorie restriction. Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.; mechanism_of_action: DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. As most DHEA is produced by the zona reticularis of the adrenal cortex, it is argued that there is a role in the immune and stress response. DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia as it is produced nearly entirely by the adrenal glands. Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.; toxicity: Acute oral toxicity (LD50): >10000 mg/kg [Rat]. Lowest Published Toxic Dose (TDL) [Man] - Route: Oral; Dose: 10 mg/kg/2W intermittent.; metabolism: Hepatic. As shown by their high conversion ratios (in a study involving cynomolgus monkeys), the major circulating metabolites of DHEA are DHEA-S, androsterone glucuronide, and androstane-3 alpha,17 beta-diol-glucuronide. [PMID: 12970301]; absorption: Following a 50-mg DHEA PO dose in cynomolgus monkeys, systemic availability was only 3.1 +/- 0.4%. [PMID: 12970301]; half_life: 12 hours; _drug_name: Prasterone.", + "drugbank_id: DB09209; indication: Pholcodine is indicated as a cough suppressant for the temporary relief of non-productive dry cough. It is stated to present a required label indication of \"temporary relief of dry cough.\"[L1200] Cough is the respiratory movement that occurs after an irritation signal is transmitted to the central nervous system and further stimulates the medulla oblongata. This stimulation causes a motor output that is sent through motoneurons to the respiratory muscles. A non-productive cough is a type of cough characterized by the absence of sputum, and it has a large inspiration that will cause continuous coughing.; pharmacodynamics: The therapeutic doses of pholcodine have been shown not to cause depression of respiration, CNS excitation or other side effects associated with narcotics. It is thought that the impact of pholcodine is selective on the cough center without affecting the respiratory center. Pholcodine is not euphorigenic, and thus, psychological dependence is unlikely. Clinical trials have not shown any evidence of addiction after prolonged administration of pholcodine.[L1201] It is well reported that pholcodine presents a more considerable respiratory depression effect than codeine and it causes hypotension in the same degree than codeine. Some other noted impacts of pholcodine in preclinical trials are: 1) the induction of histamine release, 2) anti-histaminic effect, 3) anti-acetylcholinic action, 4) anti-convulsant action and 5) mild tranquilizing action.[L1202]; mechanism_of_action: The mechanism of action of pholcodine is directly performed in the medulla oblongata. In this site, it exerts analgesic properties on the peripheric reflexogenic receptors. This site is commonly known as the \"cough center.\"[L1202]; toxicity: Generally, pholcodine is significantly less toxic than codeine. Nonetheless, it is important to consider the significant depressive respiratory effect.[L1202]; metabolism: The metabolism of pholcodine seems to be very slow[A31747] and due to the elimination profile, it is thought that most of the administered dose undergoes metabolism. There is some evidence in preclinical trials that indicate that morphine is a minor metabolite of pholcodine and that it accounts for 1% of the administered dose.[A31738] ; absorption: After oral administration of 60 mg of pholcodine, the Tmax and Cmax are reported to be 1.3 hours and 26.3 ng/ml. In the same administration, the AUC in plasma and saliva are reported to be 1.67 and 6.61 mg h/l respectively. The absorption of pholcodine is reported to represent approximately 88% of the administered dose.[A31738]; half_life: After oral administration of 60 mg of pholcodine, the half-life in plasma, saliva and urine are 45, 55 and 45 hours respectively.[A31738]; protein_binding: The protein binding of pholcodine is of approximately of 21-23% and it tends to have a slight variation depending if the administration is chronic.[A31738]; route_of_elimination: After oral administration of pholcodine, the serum concentration peaks and declines in a monoexponential manner. The percent of the dose excreted unchanged is of approximately 25-30%. Part of the administered dose is composed by metabolites that can be recovered in urine. From the administered dose, the fecal excretion corresponds to the 5% of the administered dose as unchanged pholcodine.[A31738] ; volume_of_distribution: The reported volume of distribution depends on the pharmacokinetic model and it can be of 265L based on a one-compartment model to 3207L in a two-compartment model.[A31747]; clearance: After oral administration of 60 mg of pholcodine, the clearance rate was reported to be 126 ml/min.[A31738]; _drug_name: Pholcodine.", + "drugbank_id: DB11079; indication: Indicated for the temporary relief of aches, and pains of muscles and joints associated with backache, lumbago, strains, bruises, sprains and arthritic or rheumatic pain, pain of tendons and ligaments [L1791].; pharmacodynamics: Trolamine salicylate is a salicylate that inhibits cyclo-oxygenase (COX) enzymes responsible for generating pro-inflammatory factors such as to induce pain and inflammation. It is thought to mediate its analgesic effect through inhibition of COX-2 enzyme, which is an induced enzyme responsible for inflammatory responses and pain in muscle and joint disorders. By inhibiting fatty acid COX enzyme, trolamine salicylate inhibits the production of prostaglandins and thromboxanes in inflammatory cells involved in generating pain and inflammation [T28]. It thereby works to temporarily reduce mild to moderate pain. In subjects with muscle soreness from exercise, administration of topical trolamine salicylate was associated with reduced duration and severity of muscule soreness compared to placebo [A32189]. In subjects with osteoarthritis in hands, trolamine salicylate cream was shown to be effective in achieving temporary relief of minor pain and stiffness [A32188].; mechanism_of_action: Inflammation and tissue damage in different conditions including arthritis, bursitis, joint disorder, bruises, and strains or sprains of muscle origin, induce mild to moderate pain and are associated with increase prostaglandin synthesis [T28]. This is thought to be a result of COX-2 enzyme induction. COX-2 is induced in inflammatory cells in case of cell injury, infection or activation from inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α. Upon activation, COX-2 produces prostanoid mediators of inflammation such as prostaglandins and thromboxanes [T28]. Trolamine salicylate mediates its analgesic effect by inhibiting the production of inflammatory mediators that sensitize nociceptive nerve endings and generate pain [T28].; toxicity: It is hazardous in case of ingestion [MSDS]. The carcinogenicity, mutagenicity and effects on reproductive fertility of trolamine salicylate have not been reported. ; absorption: Following topical administration of 10% trolamine salicylate in healthy volunteers, salicylic acid could not be detected in serum indicating low systemic absorption [A32190].; route_of_elimination: Following topical administration of 10% trolamine salicylate in healthy volunteers, urinary recovery of total salicylate during the first 24 hours was 6.9 mg (p < 0.05), which is 1.4% of total dose [A32190]. ; volume_of_distribution: Topical administration of 1 gram of 10% trolamine salicylate in abdominal rat skin resulted in an approximate extravascular volume of distribution (V/F) of 24.0 mL [A32191].; _drug_name: Trolamine salicylate.", + "drugbank_id: DB06649; indication: Investigated for use/treatment in pain (acute or chronic).; _drug_name: Priralfinamide.", + "drugbank_id: DB12366; indication: Indicated in pediatric and adult patients for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome).; pharmacodynamics: In all patients evaluated, MEPSEVII treatment resulted in reduction of urinary excretion of GAGs including chondroitin sulfate and dermatan sulfate, which was sustained with continued treatment [FDA Label].; mechanism_of_action: Beta-glucuronidase (GUS) is a lysosomal enzyme responsible for degradation of glucuronate-containing glycosaminoglycan (GAG) [A31278]. Resulting lysosomal storage and GAG accumulation in cells from incomplete metabolic degradation of macromolecules leads to damage to multiple tissues and organs. Vestronidase alfa serves as an exogenous source of GUS enzyme for uptake into cellular lysosomes, which is facilitated by the presence of mannose-6-phosphate (M6P) residues on the oligosaccharide chains of the recombinant enzyme. The chains allow binding of the enzyme to cell surface receptors to promote cellular uptake, and targets the lysosomes to achieve catabolism of accumulated GAGs in affected tissues [FDA Label].; toxicity: Treatment of vestronidase alfa with doses up to 20 mg/kg administered weekly in rats did not result in adverse effect on fertility and reproductive performance of male and female rats. Studies assessing the mutagenic or carcinogenic potential of vestronidase alfa have not been performed [FDA Label]. ; metabolism: Vestronidase alfa is eliminated by nonspecific proteolytic degradation into small peptides and amino acids [FDA Label].; absorption: Serum exposures of vestronidase alfa increases in a dose-proportional manner, from 1 mg/kg (0.25 times the approved recommended dosage) to 2 mg/kg (0.5 times the approved recommended dosage), and 4 mg/kg (the recommended dosage). After repeated dosing of 4 mg/kg every other week in patients with MPS VII, the mean ± standard deviation of maximal concentration (Cmax) was 20.0 ± 8.1 mcg/mL (range: 6.6 to 34.9 mcg/mL). The mean ± standard deviation of area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) was 3440 ± 1430 mcg x min/mL (range: 1130 to 5820 mcg x min/mL) [FDA Label]. ; half_life: After repeated dosing of 4 mg/kg every other week in MPS VII patients, the mean ± standard deviation of the elimination half-life (t1/2) was 155 ± 37 minutes (range: 51 to 213 minutes) [FDA Label].; route_of_elimination: Vestronidase alfa-vjbk is not expected to be eliminated through renal or fecal excretion. No excretion studies have been conducted [FDA Label].; volume_of_distribution: After repeated dosing of 4 mg/kg every other week in MPS VII patients, the mean ± standard deviation of the total volume of distribution (Vss) was 260 ± 130 mL/kg (range: 97 to 598 mL/kg) [FDA Label].; clearance: After repeated dosing of 4 mg/kg every other week in MPS VII patients, the mean ± standard deviation of the total clearance (CL) was 1.3 ± 0.7 mL/min/kg (range: 0.6 to 3.3 mL/min/kg) [FDA Label].; _drug_name: Vestronidase alfa.", + "drugbank_id: DB00856; indication: Used, along with rest and physical therapy, to treat injuries and other painful muscular conditions. Investigated for use in trigeminal neuralgia (tic douloureux), a neuropathic disorder characterized by severe facial pain. Was investigated as a modulator of histamine release.; pharmacodynamics: Chlorphenesin is a muscle relaxant. It blocks nerve impulses (or pain sensations) that are sent to the brain. ; mechanism_of_action: The mechanism of action of chlorphenesin is not well defined, and its effects are measured mainly by subjective responses. It is known that chlorphenesin acts in the central nervous system (CNS) rather than directly on skeletal muscle.; toxicity: Symptoms of a chlorphenesin overdose include drowsiness and nausea.; metabolism: Hepatic. 85% of a dose excreted within 24 hours as the glucuronide metabolite.; absorption: Rapid and complete.; half_life: 2.3-5 hours; _drug_name: Chlorphenesin." + ] + }, + { + "example_idx": 117, + "anchor_id": 17339867342714122665, + "positive_id": 12080338509835645447, + "join_paths": [ + [ + 1, + 34, + 0.2421875 + ], + [ + 10, + 34, + 0.2392578125 + ], + [ + 3, + 34, + 0.2314453125 + ], + [ + 10, + 36, + 0.2314453125 + ], + [ + 1, + 11, + 0.2236328125 + ] + ], + "rows": [ + "Lansoprazole, a proton pump inhibitor, potently inhibits human organic anion transporter, hOAT3 (SLC22A8).", + "Lansoprazole has an asymmetric atom in its structure and is clinically administered as a racemic mixture of (R)-and (S)-enantiomers.", + "However, little is known about the stereoselective inhibitory potencies of lansoprazole against hOAT3 and its homolog, hOAT1.", + "In the present study, the stereoselective inhibitory effect of lansoprazole was evaluated using hOAT1-and hOAT3-expressing cultured cells.", + "hOAT1 and hOAT3 transported [14C]p-aminohippurate and [3H]estrone-3-sulfate (ES) with Michaelis-Menten constants of 29.8 ± 4.0 and 30.1 ± 9.0 µmol/L respectively.", + "Lansoprazole enantiomers inhibited hOAT1- and hOAT3-mediated transport of each substrate in a concentration-dependent manner.", + "The IC50 value of (S)-lansoprazole against hOAT3-mediated transport of [3H]ES (0.61 ± 0.08 µmol/L) was significantly lower than that of (R)-lansoprazole (1.75 ± 0.31 µmol/L).", + "In contrast, stereoselectivity was not demonstrated for the inhibition of hOAT1.", + "Furthermore, (S)-lansoprazole inhibited hOAT3-mediated transport of pemetrexed and methotrexate (hOAT3 substrates) more strongly than the corresponding (R)-lansoprazole.", + "This study is the first to demonstrate that the stereoselective inhibitory potency of (S)-lansoprazole against hOAT3 is greater than that of (R)-lansoprazole.", + "The present findings provide novel information about the drug interactions associated with lansoprazole.", + "Drug Interactions\nEstrone\nHEK293 Cells\nHumans\nKidney\nLansoprazole\nMethotrexate\nOrganic Anion Transport Protein 1\nOrganic Anion Transporters, Sodium-Independent\nPemetrexed\nProbenecid\nProton Pump Inhibitors\nStereoisomerism\np-Aminohippuric Acid" + ], + "sentences": [ + "name: FreAmine III; ingredients: Alanine + Arginine + Cysteine + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Magnesium acetate + Methionine + Phenylalanine + Phosphoric acid + Potassium chloride + Proline + Serine + Sodium acetate + Sodium chloride + Threonine + Tryptophan + Valine; parent_key: DB00167.", + "name: EVICEL Fibrin Sealant (Human); ingredients: Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: Berinert; ingredients: Human C1-esterase inhibitor; parent_key: DB06404.", + "name: Immune Globulin Intravenous (human) 5%; ingredients: Human immunoglobulin G; parent_key: DB00028.", + "name: Aminohippurate Sodium Pah; ingredients: Aminohippuric acid; parent_key: DB00345.", + "name: Chewable Multiple Vitamins Plus Extra C; ingredients: Ascorbic acid + Cyanocobalamin + Folic acid + Nicotinamide + Pyridoxine + Riboflavin + Thiamine + Vitamin A + Vitamin D + Vitamin E; parent_key: DB00115.", + "name: Equaline Lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Methotrexate-liq Im IV Iar Int Ivr 25mg/ml; ingredients: Methotrexate; parent_key: DB00563.", + "name: ARTISS Frozen; ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222.", + "name: Ogen 2.5; ingredients: Estrone sulfate; parent_key: DB04574.", + "name: Rheumatrex Tab 2.5mg; ingredients: Methotrexate; parent_key: DB00563.", + "name: Sandoz Lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Aminosyn; ingredients: Alanine + Arginine + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Magnesium chloride + Methionine + Phenylalanine + Potassium chloride + Proline + Serine + Sodium chloride + Sodium phosphate, dibasic, unspecified form + Threonine + Tryptophan + Tyrosine + Valine; parent_key: DB00761.", + "name: Methotrexate Dbl Inj 10mg/ml; ingredients: Methotrexate; parent_key: DB00563.", + "name: Methotrexate Tablets, USP; ingredients: Methotrexate; parent_key: DB00563.", + "name: Quixil; ingredients: Calcium chloride + Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: Methotrexate Injection BP; ingredients: Methotrexate; parent_key: DB00563.", + "name: Simply Right Lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: EVICEL Fibrin Sealant (Human); ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222.", + "name: PreNatal Vitamins Plus; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Calcium + Cholecalciferol + Copper + Cyanocobalamin + Folic acid + Iron + Niacin + Pyridoxine + Riboflavin + Thiamine + Vitamin A + Zinc; parent_key: DB00126.", + "name: Benemid Tab 500mg; ingredients: Probenecid; parent_key: DB01032.", + "name: One Daily Vitamin and Mineral Dietary Supplement; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Chromium + Copper + Cyanocobalamin + Ferrous fumarate + Folic acid + Magnesium + Manganese + Nicotinamide + Pantothenic acid + Potassium + Potassium chloride + Potassium Iodide + Pyridoxine + Riboflavin + Selenic acid + Sodium molybdate + Thiamine + Vitamin A + Zinc; parent_key: DB00121.", + "name: Smart Sense Lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Pemetrexed Accord; ingredients: Pemetrexed; parent_key: DB00642.", + "name: Sunmark Lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Hp-pac; ingredients: Amoxicillin + Clarithromycin + Lansoprazole; parent_key: DB01060.", + "name: Afrezza; ingredients: Insulin human; parent_key: DB00030.", + "name: Lansoprazole 24 HR; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Pemetrexed Medac; ingredients: Pemetrexed; parent_key: DB00642.", + "name: Potassium 20meq 5% Dextrose and 0.33% Sodium Chloride; ingredients: Dextrose, unspecified form + Potassium chloride + Sodium chloride; parent_key: DB00761.", + "name: Pro Biosan Kit; ingredients: Ampicillin + Probenecid; parent_key: DB01032.", + "name: Prevacid; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Apo-lansoprazole-amoxicillin-clarithromycin; ingredients: Amoxicillin + Clarithromycin + Lansoprazole; parent_key: DB01211.", + "name: Leader lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Dg Health Lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Methotrexate Sodium Inj 25mg/ml USP; ingredients: Methotrexate; parent_key: DB00563.", + "name: Good Neighbor Pharmacy Lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Gammaplex; ingredients: Human immunoglobulin G; parent_key: DB00028.", + "name: Novolin R; ingredients: Insulin human; parent_key: DB00030.", + "name: Jamp-methotrexate; ingredients: Methotrexate; parent_key: DB00563.", + "name: Metoject Subcutaneous; ingredients: Methotrexate; parent_key: DB00563.", + "name: Concept OB; ingredients: Ascorbic acid + Biotin + Cupric sulfate + Cyanocobalamin + Ferrous fumarate + Folic acid + Iron + Magnesium sulfate + Manganese + Niacin + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Zinc sulfate, unspecified form; parent_key: DB00165.", + "name: Luna Vitamin and Mineral Bar for Women; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Chromium + Cyanocobalamin + Ferrous fumarate + Folic acid + Magnesium + Manganese + Niacin + Pantothenic acid + Potassium Iodide + Pyridoxine + Riboflavin + Selenium + Sodium molybdate + Thiamine + Vitamin E + Zinc; parent_key: DB00627.", + "name: TL-Fluorivite; ingredients: Ascorbic acid + Biotin + Copper + Cyanocobalamin + Folic acid + Iron + Magnesium + Niacin + Pantothenic acid + Pyridoxine + Riboflavin + Sodium fluoride + Thiamine + Vitamin A + Vitamin D + Vitamin E + Zinc; parent_key: DB00115.", + "name: Gammaked; ingredients: Human immunoglobulin G; parent_key: DB00028.", + "name: Apo-lansoprazole; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Artiss; ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222.", + "name: Prevacid Fastab; ingredients: Lansoprazole; parent_key: DB00448.", + "name: Raplixa; ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222.", + "name: TachoSil; ingredients: Fibrinogen human + Human thrombin; parent_key: DB09222." + ] + }, + { + "example_idx": 118, + "anchor_id": 7377366945482350633, + "positive_id": 5477779139320524493, + "join_paths": [ + [ + 6, + 39, + 0.19921875 + ], + [ + 1, + 39, + 0.18359375 + ], + [ + 0, + 39, + 0.16796875 + ], + [ + 4, + 39, + 0.1640625 + ], + [ + 6, + 14, + 0.1552734375 + ] + ], + "rows": [ + "Doses of sufentanil (i.e., 0.01, 0.04, 0.16, 0.63, 2.5, 10, and 40 micrograms/rat) were injected either into the lumbar epidural space or intravenously in rats weighing +/- 250 g, and in vivo pharmacologic activities (i.e., prolongation of latency to tail withdrawal in response to noxious heat, blockade of cornea and pinna reflexes, increase of skeletal muscle tone), ex vivo mu-opiate receptor binding (i.e., displacement of specific 3H-sufentanil binding in thalamus, striatum, hippocampus, cortex, mamillary body-medulla oblongata segment, medulla oblongata, and in cervical, thoracic, and lumbar spinal cord), and drug concentrations in plasma, brain, cortex, and cerebellum, were determined.", + "An ED50 dose of intravenous sufentanil of 0.075 micrograms/rat produced analgesia.", + "CNS-mediated in vivo side effects (i.e., blockade of pinna and cornea reflexes, muscle rigidity) were apparent at 6-28 times higher doses.", + "Epidural sufentanil also produced analgesia at an ED50 dose of 0.08 micrograms/rat, but CNS-mediated side effects occurred only at 35 to 76 times higher doses.", + "This greater in vivo selectivity of epidural sufentanil in producing analgesia was consistent with ex vivo binding data that showed that in most areas of brain, but not in spinal cord, more mu-opiate binding occurs with intravenous than with epidural sufentanil.", + "The two routes nonetheless differed by no more than a factor of approximately two in producing detectable levels of sufentanil both in plasma and in brain tissue.", + "(ABSTRACT TRUNCATED AT 250 WORDS)\nAnalgesia\nAnalgesics\nAnimals\nBrain\nEpidural Space\nFentanyl\nInjections, Intravenous\nMale\nRadioligand Assay\nRats\nRats, Inbred Strains\nReceptors, Opioid\nSpinal Cord\nSufentanil" + ], + "sentences": [ + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 8; parent_key: DB01175.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: no; position: 5; parent_key: DB01151.", + "id: BE0004702; name: Hyaluronan mediated motility receptor; organism: Humans; known_action: yes; position: 3; parent_key: DB08818.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: unknown; position: 2; parent_key: DB12808.", + "id: BE0001088; name: Tissue-type plasminogen activator; organism: Humans; known_action: yes; parent_key: DB00513.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 14; parent_key: DB00477.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 17; parent_key: DB00543.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 19; parent_key: DB06148.", + "id: BE0000687; name: Thyroid hormone receptor alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB03176.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB00370.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 13; parent_key: DB00477.", + "id: BE0000067; name: Nitric oxide synthase, brain; organism: Humans; known_action: unknown; parent_key: DB06096.", + "id: BE0000967; name: Tissue factor pathway inhibitor; organism: Humans; known_action: unknown; parent_key: DB00036.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB06678.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 7; parent_key: DB01186.", + "id: BE0003394; name: Brain-derived neurotrophic factor; organism: Humans; known_action: unknown; position: 8; parent_key: DB11823.", + "id: BE0000067; name: Nitric oxide synthase, brain; organism: Humans; known_action: unknown; position: 2; parent_key: DB03707.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 16; parent_key: DB01224.", + "id: BE0002458; name: Plasma protease C1 inhibitor; organism: Humans; known_action: unknown; parent_key: DB05961.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB13025.", + "id: BE0000364; name: Coagulation factor IX; organism: Humans; known_action: yes; position: 1; parent_key: DB09109.", + "id: BE0000241; name: Adenosine receptor A2b; organism: Humans; known_action: unknown; parent_key: DB05936.", + "id: BE0002440; name: Plasma kallikrein; organism: Humans; known_action: yes; position: 3; parent_key: DB06404.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB09194.", + "id: BE0002440; name: Plasma kallikrein; organism: Humans; known_action: unknown; position: 71; parent_key: DB14548.", + "id: BE0002440; name: Plasma kallikrein; organism: Humans; known_action: unknown; position: 96; parent_key: DB14487.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 5; parent_key: DB13025.", + "id: BE0000967; name: Tissue factor pathway inhibitor; organism: Humans; known_action: yes; position: 3; parent_key: DB06779.", + "id: BE0002150; name: Glycogen phosphorylase, brain form; organism: Humans; known_action: unknown; position: 35; parent_key: DB00114.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: no; position: 4; parent_key: DB12141.", + "id: BE0001088; name: Tissue-type plasminogen activator; organism: Humans; known_action: yes; position: 7; parent_key: DB09228.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 4; parent_key: DB09195.", + "id: BE0002112; name: Plasma serine protease inhibitor; organism: Humans; known_action: unknown; parent_key: DB00055.", + "id: BE0000767; name: Epidermal growth factor receptor; organism: Humans; known_action: yes; parent_key: DB00317.", + "id: BE0000123; name: Estrogen receptor alpha; organism: Humans; known_action: unknown; position: 14; parent_key: DB14487.", + "id: BE0000067; name: Nitric oxide synthase, brain; organism: Humans; known_action: unknown; position: 1; parent_key: DB08019.", + "id: BE0001178; name: Tissue factor; organism: Humans; known_action: unknown; parent_key: DB06552.", + "id: BE0001178; name: Tissue factor; organism: Humans; known_action: unknown; position: 2; parent_key: DB07207.", + "id: BE0002440; name: Plasma kallikrein; organism: Humans; known_action: yes; position: 4; parent_key: DB12831.", + "id: BE0000420; name: Delta-type opioid receptor; organism: Humans; known_action: unknown; parent_key: DB05050.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09194.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 8; parent_key: DB00715.", + "id: BE0003394; name: Brain-derived neurotrophic factor; organism: Humans; known_action: unknown; parent_key: DB05047.", + "id: BE0000572; name: Alpha-2B adrenergic receptor; organism: Humans; known_action: unknown; position: 18; parent_key: DB01136.", + "id: BE0003872; name: Disintegrin and metalloproteinase domain-containing protein 28; organism: Humans; known_action: unknown; parent_key: DB03088.", + "id: BE0000067; name: Nitric oxide synthase, brain; organism: Humans; known_action: unknown; position: 5; parent_key: DB00843.", + "id: BE0001178; name: Tissue factor; organism: Humans; known_action: unknown; position: 2; parent_key: DB07247.", + "id: BE0009387; name: Serine/threonine-protein kinase 35; organism: Humans; known_action: unknown; position: 26; parent_key: DB12010.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB00433.", + "id: BE0000247; name: Muscarinic acetylcholine receptor M5; organism: Humans; known_action: yes; position: 5; parent_key: DB00572." + ] + }, + { + "example_idx": 119, + "anchor_id": 12506423993271946457, + "positive_id": 5402805823941407522, + "join_paths": [ + [ + 0, + 18, + 0.28125 + ], + [ + 1, + 18, + 0.28125 + ], + [ + 1, + 20, + 0.275390625 + ], + [ + 1, + 12, + 0.228515625 + ], + [ + 1, + 43, + 0.228515625 + ] + ], + "rows": [ + "Bictegravir is a new integrase strand transfer inhibitor (INSTI) with a high genetic barrier to the development of HIV-1 resistance.", + "The drug is co-formulated with the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide (AF) in a single-tablet regimen (STR) for the once-daily treatment of HIV-1 infection in adults (bictegravir/emtricitabine/tenofovir AF; Biktarvy\nAdenine\nAdult\nAnti-HIV Agents\nDideoxynucleosides\nDose-Response Relationship, Drug\nDrug Combinations\nEmtricitabine\nHIV Infections\nHeterocyclic Compounds, 4 or More Rings\nHumans\nLamivudine\nReverse Transcriptase Inhibitors\nTreatment Outcome" + ], + "sentences": [ + "ref-id: L8225; title: Pharmaceuticals and Medical Devices Agency Japan: Report on Istradefylline; url: https://www.pmda.go.jp/files/000153870.pdf; parent_key: DB11757.", + "ref-id: L9836; title: FDA Approved Drug Products: Symtuza (Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210455s004lbl.pdf; parent_key: DB00879.", + "ref-id: L9848; title: FDA Approved Drug Products: Atripla (Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate) oral tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021937s044lbl.pdf; parent_key: DB00879.", + "ref-id: L759; title: Fablyn development history; url: http://www.drugdevelopment-technology.com/projects/lasofoxifene/; parent_key: DB06202.", + "ref-id: L10899; title: AbbVie Receives European Commission Approval of RINVOQ™ (upadacitinib) for the Treatment of Adults with Moderate to Severe Active Rheumatoid Arthritis; url: https://news.abbvie.com/news/press-releases/abbvie-receives-european-commission-approval-rinvoq-upadacitinib-for-treatment-adults-with-moderate-to-severe-active-rheumatoid-arthritis.htm; parent_key: DB15091.", + "ref-id: L6286; title: Health Canada Approved Drug Products: Tenofovir Alafenamide Oral Tablets; url: https://pdf.hres.ca/dpd_pm/00046979.PDF; parent_key: DB09299.", + "ref-id: L6337; title: European Medicines Agency Assessment Report: Tenofovir Alafenamide; url: https://www.ema.europa.eu/en/documents/assessment-report/vemlidy-epar-public-assessment-report_en.pdf; parent_key: DB09299.", + "ref-id: L1398; title: Monamine oxide inhibitors; url: http://www.inchem.org/documents/pims/pharm/pimg025.htm; parent_key: DB09244.", + "ref-id: L6277; title: FDA Approved Drug Products: Bictegravir, Emtricitabine, and Tenofovir Alafenamide Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210251s000lbl.pdf; parent_key: DB09299.", + "ref-id: L11422; title: FDA Approved Drug Products: Duetact (pioglitazone/glimepiride) oral tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021925s017lbl.pdf; parent_key: DB01132.", + "ref-id: L9839; title: FDA Approved Drug Products: Odefsey (Emtricitabine, Rilpivirine, and Tenofovir Alafenamide); url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208351s006lbl.pdf; parent_key: DB00879.", + "ref-id: L9647; title: FDA Approved Drug Products: Genvoya (Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/207561s023lbl.pdf; parent_key: DB00879.", + "ref-id: L4388; title: FDA Approved Drug Products: Descovy (Emtricitabine and Tenofovir Alafenamide) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208215s012lbl.pdf; parent_key: DB00879.", + "ref-id: L2550; title: CDC toxicological Profile for Carbon Monoxide; url: https://www.atsdr.cdc.gov/ToxProfiles/tp201-c2.pdf; parent_key: DB11588.", + "ref-id: L9587; title: FDA Approved Drug Products: Stribild (Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203100s034lbl.pdf; parent_key: DB00879.", + "ref-id: L11106; title: Neuren Pharmaceuticals: Product Development; url: http://www.neurenpharma.com/irm/content/the-science-behind-neuren-s-products1.aspx?RID=304&RedirectCount=1; parent_key: DB15601.", + "ref-id: L1221; title: BICTEGRAVIR SODIUM; url: https://pubchem.ncbi.nlm.nih.gov/compound/122197537; parent_key: DB11799.", + "ref-id: L9010; title: FDA Press Announcements: FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic; url: https://www.fda.gov/news-events/press-announcements/fda-approves-second-drug-prevent-hiv-infection-part-ongoing-efforts-end-hiv-epidemic; parent_key: DB09299.", + "ref-id: L1218; title: Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1–Infected Adults; url: https://www.researchgate.net/publication/313581562_Antiviral_Activity_Safety_and_Pharmacokinetics_of_Bictegravir_as_10-Day_Monotherapy_in_HIV-1-Infected_Adults; parent_key: DB11799.", + "ref-id: L9010; title: FDA Press Announcements: FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic; url: https://www.fda.gov/news-events/press-announcements/fda-approves-second-drug-prevent-hiv-infection-part-ongoing-efforts-end-hiv-epidemic; parent_key: DB00879.", + "ref-id: L1554; title: Trogarzo Approved to Treat Multidrug Resistant HIV-1 Infection; url: https://www.empr.com/news/trogarzo-ibalizumab-antiretroviral-multi-drug-resistant-hiv-1-infection/article/749090/; parent_key: DB12698.", + "ref-id: L2925; title: FDA Press Announcements: FDA approves a new treatment for PKU, a rare and serious genetic disease; url: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm608835.htm; parent_key: DB12839.", + "ref-id: L1580; title: Uncouplers and inhibitors; url: http://www.bmb.leeds.ac.uk/illingworth/oxphos/poisons.htm; parent_key: DB09338.", + "ref-id: L6280; title: FDA Approved Drug Products: Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207561s000lbl.pdf; parent_key: DB09299.", + "ref-id: L1350; title: Monamine Oxidase Inhibitors; url: https://books.google.ca/books?id=iUi5ErxyhVYC&pg=PA191&lpg=PA191&dq=moclobemide+clearance&source=bl&ots=9-XcLmfB1Y&sig=jKPdSO_2hzyh2adnG3Ap73GqEZQ&hl=en&sa=X&ved=0ahUKEwiPxOSHgrXZAhUY5WMKHeVgCk44ChDoAQgoMAA#v=onepage&q=moclobemide%20clearance&f=false; parent_key: DB01171.", + "ref-id: L1220; title: FDA APPROVES BIKTARVY; url: https://www.drugs.com/newdrugs/fda-approves-biktarvy-bictegravir-emtricitabine-tenofovir-alafenamide-hiv-1-infection-4691.html; parent_key: DB11799.", + "ref-id: L9842; title: FDA Approved Drug Products: Complera (Emtricitabine, Rilpivirine, Tenofovir Disoproxil Fumarate) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202123s029lbl.pdf; parent_key: DB00879.", + "ref-id: L1400; title: Screening study for genetic polymorphisms af­fecting pharmacokinetics of talnifumate; url: http://www.tcpharm.org/Data/Journal/2/349.pdf; parent_key: DB09295.", + "ref-id: L1607; title: Hormone resistance and other metabolic paradoxes; url: https://books.google.ca/books?id=KHQoBgAAQBAJ&pg=PT109&lpg=PT109&dq=tyropaque&source=bl&ots=DF-bIZuEq8&sig=rdB3GxcKY7SMBz4XBXhZwL7N84g&hl=en&sa=X&ved=0ahUKEwjA0vPIj-DZAhUEx2MKHcZGAcI4ChDoAQg1MAM#v=onepage&q=tyropaque&f=false; parent_key: DB09340.", + "ref-id: L1559; title: Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711820/; parent_key: DB12698.", + "ref-id: L11740; title: Dailymed: Trovan (trovafloxacin mesylate) oral tablet; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da9b26bb-d2d7-4113-a0f9-c6c2280f4875; parent_key: DB00685.", + "ref-id: L1219; title: BICTEGRAVIR; url: https://aidsinfo.nih.gov/drugs/print/570/bictegravir/0/1/professional; parent_key: DB11799.", + "ref-id: L6520; title: Ketorolac for Pain Management: A Review of the Clinical Evidence); url: https://www.ncbi.nlm.nih.gov/books/NBK254117/pdf/Bookshelf_NBK254117.pdf; parent_key: DB00465.", + "ref-id: L9845; title: FDA Approved Drug Products: Biktarvy (Bictegravir, Emtricitabine, and Tenofovir Alafenamide) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210251s006lbl.pdf; parent_key: DB00879.", + "ref-id: L9818; title: Cayman Chemicals: Emtricitabine MSDS; url: https://www.caymanchem.com/msdss/16879m.pdf; parent_key: DB00879.", + "ref-id: L1671; title: Thimerosal and Vaccines; url: https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228; parent_key: DB11590.", + "ref-id: L1301; title: PRECLINICAL AND CLINCIAL DEVELOPMENT OF DEXOKETOPROFEN; url: https://link.springer.com/article/10.2165/00003495-199600525-00005; parent_key: DB09214.", + "ref-id: L1509; title: New zealand perfalgan report; url: http://www.medsafe.govt.nz/profs/datasheet/p/Perfalganinf.pdf; parent_key: DB09288.", + "ref-id: L9019; title: FDA Approved Drug Products: Emtriva (Emtricitabine) Oral Capsules; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021500s029lbl.pdf; parent_key: DB00879.", + "ref-id: L6277; title: FDA Approved Drug Products: Bictegravir, Emtricitabine, and Tenofovir Alafenamide Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210251s000lbl.pdf; parent_key: DB14126.", + "ref-id: L9833; title: FDA Approved Drug Products: Truvada (Emtricitabine and Tenofovir Disoproxil Fumarate) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021752s055lbl.pdf; parent_key: DB00879.", + "ref-id: L6283; title: FDA Approved Drug Products: Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210455s000lbl.pdf; parent_key: DB09299.", + "ref-id: L1374; title: Relationship between pharmacokinetics and pharmacodynamics of molsidomine and its metabolites in humans; url: http://europepmc.org/abstract/med/3838400; parent_key: DB09282.", + "ref-id: L4388; title: FDA Approved Drug Products: Descovy (Emtricitabine and Tenofovir Alafenamide) Oral Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208215s012lbl.pdf; parent_key: DB09299.", + "ref-id: L1365; title: New Zealand report; url: http://www.medsafe.govt.nz/profs/Datasheet/n/nardiltab.pdf; parent_key: DB00780.", + "ref-id: L2429; title: U.S. Food & Drug Administration: High-Intensity Sweeteners; url: https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm397716.htm; parent_key: DB09419.", + "ref-id: L11425; title: FDA Approved Drug Products: Oseni (pioglitazone/alogliptin) oral tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022426s012lbl.pdf; parent_key: DB01132.", + "ref-id: L2962; title: Comparative Protection against Liver Inflammation and Fibrosis by a Selective Cyclooxygenase-2 Inhibitor and a Nonredox-Type 5-Lipoxygenase Inhibitor; url: http://jpet.aspetjournals.org/content/323/3/778; parent_key: DB14059.", + "ref-id: L7240; title: FDA Approved Drug Products: Catapres Clonidine Transdermal System; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018891s028lbl.pdf; parent_key: DB00575.", + "ref-id: L2966; title: Overview of selective COX-2 inhibitors; url: https://www.uptodate.com/contents/overview-of-selective-cox-2-inhibitors; parent_key: DB14059." + ] + }, + { + "example_idx": 120, + "anchor_id": 15720163471632833453, + "positive_id": 7806302483926894759, + "join_paths": [ + [ + 0, + 40, + 0.263671875 + ], + [ + 0, + 7, + 0.1923828125 + ], + [ + 1, + 6, + 0.1806640625 + ], + [ + 1, + 45, + 0.17578125 + ], + [ + 1, + 15, + 0.1728515625 + ] + ], + "rows": [ + "Cyclobenzaprine hydrochloride (CBH) is a well-known muscle relaxant that is widely used to relieve muscle spasms and other pain associated with acute musculoskeletal conditions.", + "In this study, we elucidated the binding characteristics of this muscle relaxant to human serum albumin (HSA).", + "From a pharmaceutical and biochemical viewpoint, insight into the structure, functions, dynamics, and features of HSA-CBH complex holds great importance.", + "The binding of CBH with this major circulatory transport protein was studied using a combination of biophysical approaches such as UV-VIS absorption, fluorescence quenching, and circular dichroism (CD) spectroscopy.", + "Various \nAmitriptyline\nCircular Dichroism\nHumans\nHydrophobic and Hydrophilic Interactions\nMolecular Docking Simulation\nMolecular Dynamics Simulation\nProtein Binding\nSerum Albumin, Human\nSpectrum Analysis\nThermodynamics" + ], + "sentences": [ + "name: Flexbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Macrotec; ingredients: Albumin Aggregated + Albumin human; parent_key: DB14230.", + "name: Plasbumin-25; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuminex; ingredients: Albumin human; parent_key: DB00062.", + "name: Menveo; ingredients: Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine + Meningococcal polysaccharide vaccine group A + Meningococcal polysaccharide vaccine group C + Meningococcal polysaccharide vaccine group W-135 + Meningococcal polysaccharide vaccine group Y; parent_key: DB13888.", + "name: Sterile Diluent for Allergenic Extracts Normal Saline With Hsa; ingredients: Albumin human; parent_key: DB00062.", + "name: Human Albumin Grifols 20%; ingredients: Albumin human; parent_key: DB00062.", + "name: Riva-cyclobenzaprine; ingredients: Cyclobenzaprine; parent_key: DB00924.", + "name: Albuminar-25; ingredients: Albumin human; parent_key: DB00062.", + "name: Albutein 25% Soln USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Jeanatope; ingredients: Albumin iodinated I-125 serum; parent_key: DB09429.", + "name: Albunex; ingredients: Albumin human; parent_key: DB00062.", + "name: PR Natal 430 ec; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Ferrous bisglycinate + Folic acid + Iron protein succinylate + Magnesium oxide + Nicotinamide + Omega-3 fatty acids + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB00140.", + "name: Alburex - 5; ingredients: Albumin human; parent_key: DB00062.", + "name: Megatope; ingredients: Albumin iodinated I-131 serum; parent_key: DB09430.", + "name: Human Albumin Grifols; ingredients: Albumin human; parent_key: DB00062.", + "name: Albumin (human) 5% Solution; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuminar-20; ingredients: Albumin human; parent_key: DB00062.", + "name: Exubera; ingredients: Insulin human; parent_key: DB00030.", + "name: Octalbin 5%; ingredients: Albumin human; parent_key: DB00062.", + "name: Mixed Vespid hymenoptera venom Venomil Maintenance; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11030.", + "name: Albumin (human) 25% Solution; ingredients: Albumin human; parent_key: DB00062.", + "name: Kedrab; ingredients: Human rabies virus immune globulin; parent_key: DB11603.", + "name: Alburex - 25; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuminar-5; ingredients: Albumin human; parent_key: DB00062.", + "name: Buminate 25%; ingredients: Albumin human; parent_key: DB00062.", + "name: Buminate; ingredients: Albumin human; parent_key: DB00062.", + "name: AlbuRx; ingredients: Albumin human; parent_key: DB00062.", + "name: Albutein; ingredients: Albumin human; parent_key: DB00062.", + "name: Albumin (human) 25% Solution USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Macrotec; ingredients: Albumin Aggregated + Albumin human; parent_key: DB00062.", + "name: Albutein 5% Soln USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Kedbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Optison; ingredients: Albumin human; parent_key: DB00062.", + "name: Octalbin 25%; ingredients: Albumin human; parent_key: DB00062.", + "name: ARTISS Frozen; ingredients: Fibrinogen human + Human thrombin; parent_key: DB11571.", + "name: Sterile Diluent for Allergenic Extract - Albumin Saline With Phenol; ingredients: Albumin human; parent_key: DB00062.", + "name: Bexsero; ingredients: Neisseria meningitidis serogroup b fhbp fusion protein antigen + Neisseria meningitidis serogroup b nada protein antigen + Neisseria meningitidis serogroup b nhba fusion protein antigen + Neisseria meningitidis serogroup B strain NZ98/254 outer membrane vesicle; parent_key: DB10786.", + "name: Plasmanate; ingredients: Albumin human; parent_key: DB00062.", + "name: Albumin (human) 5% Solution, USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Cyclobenzaprine Hyrochloride; ingredients: Cyclobenzaprine; parent_key: DB00924.", + "name: Plasbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Buminate 5%; ingredients: Albumin human; parent_key: DB00062.", + "name: Albumin (Human); ingredients: Albumin human; parent_key: DB00062.", + "name: Plasbumin-5; ingredients: Albumin human; parent_key: DB00062.", + "name: Normal Serum Albumin Human 25% USP; ingredients: Albumin human; parent_key: DB00062.", + "name: Volumex; ingredients: Albumin iodinated I-131 serum; parent_key: DB09430.", + "name: Triveen-Duo DHA; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Doconexent + Ferrous bisglycinate + Folic acid + Iron protein succinylate + Magnesium oxide + Nicotinamide + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB03756.", + "name: Albuked; ingredients: Albumin human; parent_key: DB00062.", + "name: Diluent for Allergenic Extract Sterile Albumin Saline With Phenol; ingredients: Albumin human; parent_key: DB00062." + ] + }, + { + "example_idx": 121, + "anchor_id": 7480300799824895934, + "positive_id": 9988049226709208946, + "join_paths": [ + [ + 1, + 9, + 0.3125 + ], + [ + 0, + 9, + 0.2890625 + ], + [ + 1, + 11, + 0.275390625 + ], + [ + 0, + 37, + 0.267578125 + ], + [ + 0, + 11, + 0.255859375 + ] + ], + "rows": [ + "Binding of the contraceptive steroids medroxyprogesterone acetate and ethynyloestradiol in blood of various species.", + "Animals\nBlood Proteins\nDogs\nEthinyl Estradiol\nGuinea Pigs\nHumans\nMacaca mulatta\nMedroxyprogesterone\nMedroxyprogesterone Acetate\nPapio\nProtein Binding\nRabbits\nRats\nSpecies Specificity" + ], + "sentences": [ + "name: Climara 50; ingredients: Estradiol; parent_key: DB00783.", + "name: Vitaday Junior Tab; ingredients: Ascorbic acid + Cholecalciferol + Cyanocobalamin + DL-alpha tocopheryl acetate + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Vitamin A; parent_key: DB00126.", + "name: Depo-provera Sterile Aqueous Suspension 150 mg/ml; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: CombiPatch (estradiol/norethindrone acetate transdermal system); ingredients: Estradiol + Norethisterone; parent_key: DB00717.", + "name: Activella; ingredients: Estradiol + Norethisterone; parent_key: DB00783.", + "name: Activelle; ingredients: Estradiol + Norethisterone; parent_key: DB00783.", + "name: Sandoz Estradiol Derm 75; ingredients: Estradiol; parent_key: DB00783.", + "name: Ceprotin; ingredients: Protein C; parent_key: DB11312.", + "name: UltraTag RBC; ingredients: Technetium Tc-99m red blood cells; parent_key: DB09493.", + "name: Medroxyprogesterone; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: Estraderm-25; ingredients: Estradiol; parent_key: DB00783.", + "name: Medroxyprogesterone Acetate Injectable Suspension USP; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: Activelle Ld; ingredients: Estradiol + Norethisterone; parent_key: DB00783.", + "name: Climara 25; ingredients: Estradiol; parent_key: DB00783.", + "name: Olimel 4.4% E; ingredients: Alanine + Arginine + Aspartic acid + Calcium chloride + Dextrose, unspecified form + Glutamic acid + Glycine + Histidine + Isoleucine + L-Lysine + Leucine + Magnesium chloride + Methionine + Olive oil + Phenylalanine + Potassium chloride + Proline + Serine + Sodium acetate + Sodium glycerophosphate + Soybean oil + Threonine + Tryptophan + Tyrosine + Valine; parent_key: DB00167.", + "name: Estalis Sequi; ingredients: Estradiol + Estradiol + Norethisterone; parent_key: DB00717.", + "name: Imvexxy; ingredients: Estradiol; parent_key: DB00783.", + "name: Estradiol and Norethindrone Acetate; ingredients: Estradiol + Norethisterone; parent_key: DB00717.", + "name: Estradiol Vaginal Inserts; ingredients: Estradiol; parent_key: DB00783.", + "name: Estrace Tab 2mg; ingredients: Estradiol; parent_key: DB00783.", + "name: Provera 2.5mg Tablets; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: Femtrace; ingredients: Estradiol acetate; parent_key: DB13952.", + "name: Femring; ingredients: Estradiol acetate; parent_key: DB13952.", + "name: Vitamin & Mineral Formula 1 Dietary Supplement; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Calcium + Cholecalciferol + Choline + Copper + Cyanocobalamin + Ferrous gluconate + Folic acid + Inositol + Iodine + Manganese + Niacin + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Vitamin A + Zinc; parent_key: DB00126.", + "name: Oesclim; ingredients: Estradiol; parent_key: DB00783.", + "name: Estradiol Vaginal; ingredients: Estradiol; parent_key: DB00783.", + "name: Provera 10mg Tablets; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: Minivelle; ingredients: Estradiol; parent_key: DB00783.", + "name: Prenatvite Plus; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Boron + Calcium + Cholecalciferol + Citrus bioflavonoids + Cupric oxide + Cyanocobalamin + Ferrous fumarate + Folic acid + Inositol + Nicotinamide + Pyridoxine + Riboflavin + Thiamine + Vitamin A + Zinc oxide; parent_key: DB00152.", + "name: Estradiol -Micronized; ingredients: Estradiol; parent_key: DB00783.", + "name: Vitafol Fe Plus; ingredients: Ascorbic acid + Beta carotene + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Doconexent + Folic acid + Iron + Levomefolic acid + Magnesium oxide + Nicotinamide + Potassium Iodide + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB00169.", + "name: Vivelle 37.5mcg; ingredients: Estradiol; parent_key: DB00783.", + "name: Cavan Folate DHA; ingredients: Ascorbic acid + Ascorbic acid + Beta carotene + Beta carotene + Calcium carbonate + Calcium carbonate + Cholecalciferol + Cholecalciferol + Cupric oxide + Cupric oxide + Cyanocobalamin + Cyanocobalamin + DL-alpha tocopheryl acetate + DL-alpha tocopheryl acetate + Doconexent + Doconexent + Ferrous fumarate + Ferrous fumarate + Folic acid + Folic acid + Magnesium oxide + Magnesium oxide + Nicotinamide + Nicotinamide + Pyridoxine + Pyridoxine + Riboflavin + Riboflavin + Thiamine + Thiamine + Zinc oxide + Zinc oxide; parent_key: DB00140.", + "name: Vivelle 50mcg; ingredients: Estradiol; parent_key: DB00783.", + "name: Estra-25; ingredients: Estradiol; parent_key: DB00783.", + "name: Proclim; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: Marnatal F; ingredients: Ascorbic acid + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + D-alpha-Tocopherol acetate + Folic acid + Iron sucrose + Magnesium oxide + Nicotinamide + Pyridoxine + Riboflavin + Thiamine; parent_key: DB00115.", + "name: Penta-medroxyprogesterone Tablets; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: Estraderm; ingredients: Estradiol; parent_key: DB00783.", + "name: Amabelz; ingredients: Estradiol + Norethisterone; parent_key: DB00717.", + "name: Estradot 37.5; ingredients: Estradiol; parent_key: DB00783.", + "name: Zoo Chews Plus Iron; ingredients: Ascorbic acid + Cyanocobalamin + DL-alpha tocopheryl acetate + Ergosterol + Ferrous fumarate + Folic acid + Nicotinamide + Pyridoxine + Riboflavin + Sodium ascorbate + Thiamine + Vitamin A; parent_key: DB00152.", + "name: Mimvey; ingredients: Estradiol + Norethisterone; parent_key: DB00783.", + "name: Activella; ingredients: Estradiol + Norethisterone; parent_key: DB00717.", + "name: Mimvey Lo; ingredients: Estradiol + Norethisterone; parent_key: DB00783.", + "name: Gen-medroxy Tablet 5mg; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: Nu-medroxy; ingredients: Medroxyprogesterone acetate; parent_key: DB00603.", + "name: Virt-Advance; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Docusate + Folic acid + Iron + Magnesium oxide + Nicotinamide + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB06755.", + "name: Prenatvite Complete; ingredients: alpha-Tocopherol acetate + Ascorbic acid + Biotin + Calcium + Cholecalciferol + Cupric oxide + Cyanocobalamin + Ferrous fumarate + Folic acid + Iodine + Magnesium oxide + Nicotinamide + Pantothenic acid + Pyridoxine + Riboflavin + Thiamine + Vitamin A + Zinc oxide; parent_key: DB01377.", + "name: Estraderm-100; ingredients: Estradiol; parent_key: DB00783." + ] + }, + { + "example_idx": 122, + "anchor_id": 7820928641113755248, + "positive_id": 6737415077030462053, + "join_paths": [ + [ + 6, + 5, + 0.279296875 + ], + [ + 6, + 45, + 0.25 + ], + [ + 4, + 5, + 0.23828125 + ], + [ + 2, + 5, + 0.236328125 + ], + [ + 6, + 46, + 0.2333984375 + ] + ], + "rows": [ + "The renal clearances of acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate were determined in eight healthy adults 2 h after administration of 1.5 g of acetaminophen.", + "The renal clearance ratios (relative to creatinine) were 0.058 +/- 0.026, 0.890 +/- 0.153, and 1.43 +/- 0.250 (mean +/- SD), respectively.", + "The renal clearance of acetaminophen increased with increasing urine flow rate, and that of acetaminophen sulfate decreased with increasing serum concentration of the conjugate.", + "A strong positive correlation was found between the renal clearances of acetaminophen glucuronide and acetaminophen sulfate, possibly due to blood perfusion rate-dependent renal tubular secretion of the two conjugates.", + "The serum protein binding of acetaminophen (congruent to 20%) and acetaminophen glucuronide (less than 10%) are minor.", + "Acetaminophen sulfate is greater than 50% protein bound, as determined by equilibrium dialysis and ultrafiltration.", + "The results of these studies are (a) consistent with previous reports of animal studies, indicating that renal excretion of acetaminophen involves glomerular filtration and passive reabsorption and that acetaminophen sulfate is subject to active renal tubular secretion, and (b) compatible with the reported occurrence of renal tubular secretion of acetaminophen glucuronide in animals.", + "Acetaminophen\nAdult\nAlbumins\nBlood Proteins\nCreatinine\nFemale\nHumans\nKidney\nMale\nProtein Binding\nUltrafiltration" + ], + "sentences": [ + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Norfloxacin.; parent_key: DB01059.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Troglitazone.; parent_key: DB00197.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Cloranolol can be decreased when combined with Acetaminophen.; parent_key: DB13508.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Trazodone.; parent_key: DB00656.", + "drugbank-id: DB00316; name: Acetaminophen; description: The serum concentration of Voxelotor can be increased when it is combined with Acetaminophen.; parent_key: DB14975.", + "drugbank-id: DB00316; name: Acetaminophen; description: Acetaminophen may decrease the excretion rate of Metaxalone which could result in a higher serum level.; parent_key: DB00660.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acenocoumarol can be increased when combined with Acetaminophen.; parent_key: DB01418.", + "drugbank-id: DB00316; name: Acetaminophen; description: The risk or severity of adverse effects can be increased when Acetaminophen is combined with Warfarin.; parent_key: DB00682.", + "drugbank-id: DB08059; name: Wortmannin; description: The risk or severity of adverse effects can be increased when Etanercept is combined with Wortmannin.; parent_key: DB00005.", + "drugbank-id: DB00316; name: Acetaminophen; description: The serum concentration of Acetaminophen can be increased when it is combined with Cediranib.; parent_key: DB04849.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Adenine.; parent_key: DB00173.", + "drugbank-id: DB00316; name: Acetaminophen; description: Etomidate may decrease the excretion rate of Acetaminophen which could result in a higher serum level.; parent_key: DB00292.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Rucaparib.; parent_key: DB12332.", + "drugbank-id: DB10395; name: Holcus lanatus pollen; description: The risk of a hypersensitivity reaction to Holcus lanatus pollen is increased when it is combined with Nadolol.; parent_key: DB01203.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Revefenacin can be decreased when combined with Acetaminophen.; parent_key: DB11855.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Felodipine.; parent_key: DB01023.", + "drugbank-id: DB00316; name: Acetaminophen; description: The risk or severity of adverse effects can be increased when Acetaminophen is combined with Metamizole.; parent_key: DB04817.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Nalidixic acid.; parent_key: DB00779.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Esmirtazapine can be decreased when combined with Acetaminophen.; parent_key: DB06678.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Pibrentasvir.; parent_key: DB13878.", + "drugbank-id: DB00186; name: Lorazepam; description: Salmon calcitonin may decrease the excretion rate of Lorazepam which could result in a higher serum level.; parent_key: DB00017.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Medical Cannabis can be increased when combined with Acetaminophen.; parent_key: DB14009.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Pentifylline can be decreased when combined with Acetaminophen.; parent_key: DB13634.", + "drugbank-id: DB00316; name: Acetaminophen; description: The risk or severity of adverse effects can be increased when Acetaminophen is combined with Salsalate.; parent_key: DB01399.", + "drugbank-id: DB00316; name: Acetaminophen; description: The serum concentration of Acetaminophen can be increased when it is combined with Genistein.; parent_key: DB01645.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Lisuride can be decreased when combined with Acetaminophen.; parent_key: DB00589.", + "drugbank-id: DB00316; name: Acetaminophen; description: The risk or severity of adverse effects can be increased when Acetaminophen is combined with Balsalazide.; parent_key: DB01014.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Formoterol can be decreased when combined with Acetaminophen.; parent_key: DB00983.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Reboxetine.; parent_key: DB00234.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Cinnarizine can be decreased when combined with Acetaminophen.; parent_key: DB00568.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Thiabendazole.; parent_key: DB00730.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be decreased when combined with Pipemidic acid.; parent_key: DB13823.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Prucalopride can be decreased when combined with Acetaminophen.; parent_key: DB06480.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Allylestrenol can be increased when combined with Acetaminophen.; parent_key: DB01431.", + "drugbank-id: DB00316; name: Acetaminophen; description: Cefradine may decrease the excretion rate of Acetaminophen which could result in a higher serum level.; parent_key: DB01333.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Oxymorphone can be decreased when combined with Acetaminophen.; parent_key: DB01192.", + "drugbank-id: DB01418; name: Acenocoumarol; description: The metabolism of Acenocoumarol can be decreased when combined with Interferon alfa-n1.; parent_key: DB00011.", + "drugbank-id: DB06436; name: Semaxanib; description: The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Semaxanib.; parent_key: DB00016.", + "drugbank-id: DB12749; name: Butylphthalide; description: The risk or severity of bleeding can be increased when Butylphthalide is combined with Reteplase.; parent_key: DB00015.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be increased when combined with Dacomitinib.; parent_key: DB11963.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Encorafenib can be increased when combined with Acetaminophen.; parent_key: DB11718.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Maprotiline can be decreased when combined with Acetaminophen.; parent_key: DB00934.", + "drugbank-id: DB00316; name: Acetaminophen; description: Acetaminophen may decrease the excretion rate of Piperacillin which could result in a higher serum level.; parent_key: DB00319.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Acetaminophen can be increased when combined with Ceritinib.; parent_key: DB09063.", + "drugbank-id: DB01297; name: Practolol; description: The risk or severity of bradycardia can be increased when Magnesium sulfate is combined with Practolol.; parent_key: DB00653.", + "drugbank-id: DB00316; name: Acetaminophen; description: Acetaminophen may decrease the excretion rate of Digoxin which could result in a higher serum level.; parent_key: DB00390.", + "drugbank-id: DB00316; name: Acetaminophen; description: Acetaminophen may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB09477.", + "drugbank-id: DB00316; name: Acetaminophen; description: Acetaminophen may decrease the excretion rate of Ethambutol which could result in a higher serum level.; parent_key: DB00330.", + "drugbank-id: DB00316; name: Acetaminophen; description: The metabolism of Amiodarone can be increased when combined with Acetaminophen.; parent_key: DB01118.", + "drugbank-id: DB13527; name: Proglumetacin; description: The protein binding of Gliclazide can be decreased when combined with Proglumetacin.; parent_key: DB01120." + ] + }, + { + "example_idx": 123, + "anchor_id": 9611334685580933947, + "positive_id": 6036472277054760371, + "join_paths": [ + [ + 1, + 36, + 0.18359375 + ] + ], + "rows": [ + "Estimation of transcortin concentration by measurements of plasma protein-binding of prednisolone and by electroimmunodiffusion.", + "Blood Proteins\nHumans\nImmunodiffusion\nKidney Transplantation\nPrednisolone\nProtein Binding\nSerum Albumin\nTranscortin" + ], + "sentences": [ + "name: Albuminar-25; ingredients: Albumin human; parent_key: DB00062.", + "name: PrednisoLONE; ingredients: Prednisolone; parent_key: DB00860.", + "name: Albuminex; ingredients: Albumin human; parent_key: DB00062.", + "name: Red Kidney Beans; ingredients: Kidney bean; parent_key: DB10639.", + "name: Plasbumin-25; ingredients: Albumin human; parent_key: DB00062.", + "name: balsam peru oil PainAway with natural peppermint and Balsam Peru; ingredients: Balsam of Peru + Levomenthol; parent_key: DB11482.", + "name: Human Albumin Grifols; ingredients: Albumin human; parent_key: DB00062.", + "name: Millipred; ingredients: Prednisolone; parent_key: DB00860.", + "name: Megatope; ingredients: Albumin iodinated I-131 serum; parent_key: DB09430.", + "name: Pediapred; ingredients: Prednisolone; parent_key: DB00860.", + "name: PMS-prednisolone; ingredients: Prednisolone; parent_key: DB00860.", + "name: Wasp hymenoptera venom Multidose; ingredients: Polistes annularis venom protein + Polistes exclamans venom protein + Polistes fuscatus venom protein + Polistes metricus venom protein; parent_key: DB11028.", + "name: Plasbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuminar-20; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuminar-5; ingredients: Albumin human; parent_key: DB00062.", + "name: Hemorro-dol Sup; ingredients: Balsam of Peru + Belladonna + Benzocaine + Bismuth subcarbonate + Bismuth subnitrate + Boric acid + Ephedrine + Zinc oxide; parent_key: DB09321.", + "name: Prednisolone; ingredients: Prednisolone; parent_key: DB00860.", + "name: Pinto Bean; ingredients: Kidney bean; parent_key: DB10639.", + "name: Plasbumin-5; ingredients: Albumin human; parent_key: DB00062.", + "name: Flexbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: Octaplasma; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Albumin (Human); ingredients: Albumin human; parent_key: DB00062.", + "name: Gardasil 9; ingredients: Human papillomavirus type 11 L1 capsid protein antigen + Human papillomavirus type 16 L1 capsid protein antigen + Human papillomavirus type 18 L1 capsid protein antigen + Human papillomavirus type 31 L1 capsid protein antigen + Human papillomavirus type 33 L1 capsid protein antigen + Human papillomavirus type 45 L1 capsid protein antigen + Human papillomavirus type 52 L1 capsid protein antigen + Human papillomavirus type 58 L1 capsid protein antigen + Human papillomavirus type 6 L1 capsid protein antigen; parent_key: DB10300.", + "name: Volumex; ingredients: Albumin iodinated I-131 serum; parent_key: DB09430.", + "name: Albutein; ingredients: Albumin human; parent_key: DB00062.", + "name: Diluent for Allergenic Extract Sterile Albumin Saline With Phenol; ingredients: Albumin human; parent_key: DB00062.", + "name: Red Kidney Bean; ingredients: Kidney bean; parent_key: DB10639.", + "name: Alburex - 25; ingredients: Albumin human; parent_key: DB00062.", + "name: Kedbumin; ingredients: Albumin human; parent_key: DB00062.", + "name: AlbuRx; ingredients: Albumin human; parent_key: DB00062.", + "name: Prevnar; ingredients: Streptococcus pneumoniae type 14 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 18c capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 19f capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 23f capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 4 capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 6b capsular polysaccharide diphtheria crm197 protein conjugate antigen + Streptococcus pneumoniae type 9v capsular polysaccharide diphtheria crm197 protein conjugate antigen; parent_key: DB10289.", + "name: Octaplas; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Novo-prednisolone 5mg; ingredients: Prednisolone; parent_key: DB00860.", + "name: Pulmolite, Kit for the Preparation of Technetium Tc99m Albumin Aggregated; ingredients: Technetium Tc-99m albumin colloid; parent_key: DB09447.", + "name: White Kidney Beans; ingredients: Kidney bean; parent_key: DB10639.", + "name: PR Natal 400; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Ferrous bisglycinate + Folic acid + Iron protein succinylate + Magnesium oxide + Nicotinamide + Omega-3 fatty acids + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB01377.", + "name: Plasma Protein Fraction (human) Protenate; ingredients: Plasma protein fraction (human); parent_key: DB13968.", + "name: Plasmanate; ingredients: Albumin human; parent_key: DB00062.", + "name: Kidney Bean; ingredients: Kidney bean; parent_key: DB10639.", + "name: Pediapred - Liq 6.7mg/5ml; ingredients: Prednisolone; parent_key: DB00860.", + "name: Pred-G; ingredients: Gentamicin + Prednisolone acetate; parent_key: DB00798.", + "name: Alburex - 5; ingredients: Albumin human; parent_key: DB00062.", + "name: Octalbin 25%; ingredients: Albumin human; parent_key: DB00062.", + "name: Albuked; ingredients: Albumin human; parent_key: DB00062.", + "name: Navy Bean; ingredients: Kidney bean; parent_key: DB10639.", + "name: Buminate; ingredients: Albumin human; parent_key: DB00062.", + "name: Navy Beans; ingredients: Kidney bean; parent_key: DB10639.", + "name: Sandoz Prednisolone; ingredients: Prednisolone acetate; parent_key: DB15566.", + "name: Jeanatope; ingredients: Albumin iodinated I-125 serum; parent_key: DB09429.", + "name: PR Natal 430; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Ferrous bisglycinate + Folic acid + Iron protein succinylate + Magnesium oxide + Nicotinamide + Omega-3 fatty acids + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB02701." + ] + }, + { + "example_idx": 124, + "anchor_id": 4354790554970075567, + "positive_id": 16027710748056398510, + "join_paths": [ + [ + 9, + 38, + 0.1669921875 + ], + [ + 9, + 17, + 0.166015625 + ], + [ + 9, + 46, + 0.166015625 + ], + [ + 9, + 7, + 0.1650390625 + ], + [ + 9, + 22, + 0.1650390625 + ] + ], + "rows": [ + "The effects of two new phthalazinone derivatives, azelastine (AZ) and flezelastine (FZ), on the reversal of resistance to doxorubicin (dox) were studied using two variants of the rat C6 glioblastoma cell line, selected with dox (C6 0.5) or with vincristine (C6 1V).", + "Both lines presented a multidrug-resistant phenotype which was, in the case of C6 0.5 cells, likely to be accompanied by an additional mechanism leading to intracellular tolerance of the drug.", + "Both AZ and FZ reversed dox resistance in a concentration-dependent manner, and FZ was shown to be at least three times more potent than AZ.", + "FZ was able, at a relatively high concentration (30 microM), to completely restore dox sensitivity in both cell lines.", + "Both drugs were able to virtually restore dox accumulation to the level reached in sensitive cells, and, interestingly, this complete restoration occurred at lower concentrations of modulator than required for complete reversal of resistance.", + "FZ was able to reverse dox intracellular tolerance of C6 0.5 cells and to restore dox accumulation at the IC50 to the level observed in sensitive cells.", + "AZ and FZ both inhibited azidopine binding to membrane preparations of C6 0.5 and C6 1V cells, although FZ was more potent.", + "Both drugs more successfully inhibited azidopine binding to membranes prepared from C6 1V cells (which express the mdr1b gene product) than to membranes from C6 0.5 cells (which express the mdr1a gene product).", + "In view of its potent activity on MDR, further preclinical evaluation of FZ is warranted.", + "ATP Binding Cassette Transporter, Subfamily B, Member 1\nAnimals\nAzepines\nAzides\nDihydropyridines\nDose-Response Relationship, Drug\nDoxorubicin\nDrug Resistance, Multiple\nPhthalazines\nRats\nTumor Cells, Cultured\nVincristine" + ], + "sentences": [ + "id: BE0002369; name: ATP-binding cassette sub-family B member 5; organism: Humans; known_action: unknown; position: 1; parent_key: DB13997.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB06654.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 6; parent_key: DB09074.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 8; parent_key: DB01079.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB08828.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00973.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 8; parent_key: DB12483.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB00602.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00444.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 14; parent_key: DB00544.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB01017.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 10; parent_key: DB01248.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB09274.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 15; parent_key: DB00688.", + "id: BE0002369; name: ATP-binding cassette sub-family B member 5; organism: Humans; known_action: no; position: 9; parent_key: DB04948.", + "id: BE0001069; name: Canalicular multispecific organic anion transporter 1; organism: Humans; known_action: unknown; position: 3; parent_key: DB11770.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 6; parent_key: DB09073.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 11; parent_key: DB00220.", + "id: BE0003657; name: Multidrug and toxin extrusion protein 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB01333.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB08912.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB04690.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: no; position: 1; parent_key: DB13092.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 5; parent_key: DB15091.", + "id: BE0000276; name: Solute carrier family 12 member 7; organism: Humans; known_action: unknown; position: 5; parent_key: DB00761.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 19; parent_key: DB13955.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB01094.", + "id: BE0001069; name: Canalicular multispecific organic anion transporter 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00795.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB00740.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB13125.", + "id: BE0000879; name: Solute carrier family 22 member 11; organism: Humans; known_action: unknown; position: 18; parent_key: DB01032.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB00795.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB08916.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB09279.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 6; parent_key: DB11613.", + "id: BE0005055; name: Sodium-dependent phosphate transporter 1; organism: Humans; known_action: no; position: 1; parent_key: DB14503.", + "id: BE0000785; name: Multidrug resistance-associated protein 1; organism: Humans; known_action: unknown; position: 2; parent_key: DB01045.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00437.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 9; parent_key: DB06290.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 13; parent_key: DB14962.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: no; position: 13; parent_key: DB12267.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB11901.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB09038.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB11827.", + "id: BE0003647; name: Solute carrier family 22 member 2; organism: Humans; known_action: unknown; position: 19; parent_key: DB13874.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00285.", + "id: BE0002369; name: ATP-binding cassette sub-family B member 5; organism: Humans; known_action: unknown; position: 3; parent_key: DB08870.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 3; parent_key: DB11732.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 5; parent_key: DB00958.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 19; parent_key: DB13956.", + "id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 12; parent_key: DB14649." + ] + }, + { + "example_idx": 125, + "anchor_id": 6078515666988438927, + "positive_id": 12808158921102570022, + "join_paths": [ + [ + 0, + 33, + 0.3515625 + ], + [ + 9, + 33, + 0.349609375 + ], + [ + 7, + 33, + 0.328125 + ], + [ + 11, + 33, + 0.3203125 + ], + [ + 10, + 10, + 0.275390625 + ] + ], + "rows": [ + "Cefepime is a novel methoxyimino-aminothiazolyl cephalosporin with a quaternized N-methyl-pyrrolidine moiety at the 3' position conferring zwitterionic properties.", + "Because of this the molecule penetrates the outer cell membrane of Gram-negative bacteria rapidly.", + "In addition it is resistant to degradation by several plasmid and chromosomally-mediated beta-lactamases, for which it also shows very low affinity and no inducing capacity.", + "It has good affinity for PBPs 2 and 3 of Escherichia coli and for PBP 3 of Pseudomonas aeruginosa.", + "Its broad-spectrum of activity includes Gram-positive and Gram-negative pathogens.", + "It is more active than cefotaxime or ceftazidime, against Enterobacteriaceae.", + "The MIC90 for P. aeruginosa is higher than that of ceftazidime, but lower than those of cefpirome, cefoperazone and latamoxef.", + "Other Gram-negative organisms, Haemophilus influenzae, Neiserria meningitidis, Neiserria gonorrhoeae, Moraxella catarrhalis are highly susceptible to cefepime.", + "Among Gram-positive species methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, whether beta-lactamase producers or not, Streptococcus pneumoniae and Streptococcus pyogenes are susceptible.", + "Cefepime is active against cefotaxime- and/or ceftazidime-resistant Enterobacteriaceae.", + "Only strains of P. aeruginosa producing large amounts of beta-lactamase may be resistant to both ceftazidime and cefepime.", + "In experimental infections such as meningitis, induced with various bacterial species in neonatal rats and chronic staphylococcal osteomyelitis in rabbits, cefepime has shown good efficacy.", + "Animals\nBacteria\nBacterial Infections\nCefepime\nCephalosporins\nDrug Resistance, Microbial\nHumans\nRabbits\nRats" + ], + "sentences": [ + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Paromomycin which could result in a higher serum level.; parent_key: DB01421.", + "drugbank-id: DB00438; name: Ceftazidime; description: Bacitracin may decrease the excretion rate of Ceftazidime which could result in a higher serum level.; parent_key: DB00626.", + "drugbank-id: DB00438; name: Ceftazidime; description: Ceftazidime may decrease the excretion rate of Selenium which could result in a higher serum level.; parent_key: DB11135.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Baricitinib which could result in a higher serum level.; parent_key: DB11817.", + "drugbank-id: DB01329; name: Cefoperazone; description: Cefoperazone may decrease the excretion rate of Eszopiclone which could result in a higher serum level.; parent_key: DB00402.", + "drugbank-id: DB10389; name: Lolium perenne pollen; description: The risk of a hypersensitivity reaction to Lolium perenne pollen is increased when it is combined with Befunolol.; parent_key: DB09013.", + "drugbank-id: DB00438; name: Ceftazidime; description: Ceftazidime may decrease the excretion rate of Prasugrel which could result in a higher serum level.; parent_key: DB06209.", + "drugbank-id: DB01580; name: Oxprenolol; description: The risk of a hypersensitivity reaction to Sorghum halepense pollen is increased when it is combined with Oxprenolol.; parent_key: DB10365.", + "drugbank-id: DB00438; name: Ceftazidime; description: The risk or severity of bleeding can be increased when Ceftazidime is combined with (R)-warfarin.; parent_key: DB08496.", + "drugbank-id: DB00438; name: Ceftazidime; description: The therapeutic efficacy of Drotrecogin alfa can be decreased when used in combination with Ceftazidime.; parent_key: DB00055.", + "drugbank-id: DB00438; name: Ceftazidime; description: Cefbuperazone may decrease the excretion rate of Ceftazidime which could result in a higher serum level.; parent_key: DB13638.", + "drugbank-id: DB01021; name: Trichlormethiazide; description: Trichlormethiazide may increase the excretion rate of Leuprolide which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB00007.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Metoclopramide which could result in a higher serum level.; parent_key: DB01233.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Phenelzine which could result in a higher serum level.; parent_key: DB00780.", + "drugbank-id: DB00438; name: Ceftazidime; description: Etoricoxib may decrease the excretion rate of Ceftazidime which could result in a higher serum level.; parent_key: DB01628.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Ertapenem which could result in a higher serum level.; parent_key: DB00303.", + "drugbank-id: DB00438; name: Ceftazidime; description: Ceftazidime may decrease the excretion rate of Iopromide which could result in a higher serum level.; parent_key: DB09156.", + "drugbank-id: DB00438; name: Ceftazidime; description: Ceftazidime may decrease the excretion rate of Idarucizumab which could result in a higher serum level.; parent_key: DB09264.", + "drugbank-id: DB00438; name: Ceftazidime; description: The therapeutic efficacy of Semuloparin can be decreased when used in combination with Ceftazidime.; parent_key: DB06294.", + "drugbank-id: DB00493; name: Cefotaxime; description: The excretion of Taurocholic acid can be decreased when combined with Cefotaxime.; parent_key: DB04348.", + "drugbank-id: DB00493; name: Cefotaxime; description: The risk or severity of nephrotoxicity can be increased when Cefotaxime is combined with Atazanavir.; parent_key: DB01072.", + "drugbank-id: DB01329; name: Cefoperazone; description: Cefoperazone may decrease the excretion rate of Cyanocobalamin which could result in a higher serum level.; parent_key: DB00115.", + "drugbank-id: DB00493; name: Cefotaxime; description: The therapeutic efficacy of Tenecteplase can be decreased when used in combination with Cefotaxime.; parent_key: DB00031.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Acyclovir which could result in a higher serum level.; parent_key: DB00787.", + "drugbank-id: DB13682; name: Cefpirome; description: Cefpirome may decrease the excretion rate of Ranolazine which could result in a higher serum level.; parent_key: DB00243.", + "drugbank-id: DB13646; name: Saruplase; description: The therapeutic efficacy of Saruplase can be decreased when used in combination with Latamoxef.; parent_key: DB04570.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Digoxin which could result in a higher serum level.; parent_key: DB00390.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Piracetam which could result in a higher serum level.; parent_key: DB09210.", + "drugbank-id: DB00438; name: Ceftazidime; description: Hygromycin B may decrease the excretion rate of Ceftazidime which could result in a higher serum level.; parent_key: DB11520.", + "drugbank-id: DB00493; name: Cefotaxime; description: The therapeutic efficacy of Doramectin can be decreased when used in combination with Cefotaxime.; parent_key: DB11400.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Terbutaline which could result in a higher serum level.; parent_key: DB00871.", + "drugbank-id: DB00438; name: Ceftazidime; description: Suxibuzone may decrease the excretion rate of Ceftazidime which could result in a higher serum level.; parent_key: DB13232.", + "drugbank-id: DB00438; name: Ceftazidime; description: Ceftazidime may decrease the excretion rate of Fondaparinux which could result in a higher serum level.; parent_key: DB00569.", + "drugbank-id: DB01413; name: Cefepime; description: Cefepime may decrease the excretion rate of Metoprolol which could result in a higher serum level.; parent_key: DB00264.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Perindopril which could result in a higher serum level.; parent_key: DB00790.", + "drugbank-id: DB00620; name: Triamcinolone; description: The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Triamcinolone.; parent_key: DB00008.", + "drugbank-id: DB00493; name: Cefotaxime; description: The risk or severity of nephrotoxicity can be increased when Cefotaxime is combined with Antrafenine.; parent_key: DB01419.", + "drugbank-id: DB00438; name: Ceftazidime; description: Ceftazidime may decrease the excretion rate of Pyridoxine which could result in a higher serum level.; parent_key: DB00165.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of N-methylnicotinamide which could result in a higher serum level.; parent_key: DB08840.", + "drugbank-id: DB00493; name: Cefotaxime; description: The risk or severity of nephrotoxicity can be increased when Cefotaxime is combined with Suxibuzone.; parent_key: DB13232.", + "drugbank-id: DB00438; name: Ceftazidime; description: Atazanavir may decrease the excretion rate of Ceftazidime which could result in a higher serum level.; parent_key: DB01072.", + "drugbank-id: DB00438; name: Ceftazidime; description: Ceftazidime may decrease the excretion rate of Pralidoxime which could result in a higher serum level.; parent_key: DB00733.", + "drugbank-id: DB00254; name: Doxycycline; description: The risk or severity of bleeding can be increased when Doxycycline is combined with Urokinase.; parent_key: DB00013.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Pralidoxime which could result in a higher serum level.; parent_key: DB00733.", + "drugbank-id: DB00373; name: Timolol; description: Cefoperazone may decrease the excretion rate of Timolol which could result in a higher serum level.; parent_key: DB01329.", + "drugbank-id: DB00493; name: Cefotaxime; description: Cefotaxime may decrease the excretion rate of Pemetrexed which could result in a higher serum level.; parent_key: DB00642.", + "drugbank-id: DB01101; name: Capecitabine; description: Salmon calcitonin may decrease the excretion rate of Capecitabine which could result in a higher serum level.; parent_key: DB00017.", + "drugbank-id: DB00438; name: Ceftazidime; description: Ceftazidime may decrease the excretion rate of Trifluridine which could result in a higher serum level.; parent_key: DB00432.", + "drugbank-id: DB00438; name: Ceftazidime; description: Loxoprofen may decrease the excretion rate of Ceftazidime which could result in a higher serum level.; parent_key: DB09212.", + "drugbank-id: DB01329; name: Cefoperazone; description: Cefoperazone may decrease the excretion rate of Leuprolide which could result in a higher serum level.; parent_key: DB00007." + ] + }, + { + "example_idx": 126, + "anchor_id": 15001315663985269990, + "positive_id": 17234534610339361131, + "join_paths": [ + [ + 6, + 37, + 0.23046875 + ], + [ + 6, + 44, + 0.2294921875 + ], + [ + 6, + 45, + 0.22265625 + ], + [ + 6, + 6, + 0.2177734375 + ], + [ + 6, + 12, + 0.2138671875 + ] + ], + "rows": [ + "A fluorescent vinblastine derivative, vinblastine-4'-anthranilate, has been shown to inhibit polymerization of rat brain tubulin (IC50 = 4.8 microM).", + "Binding of the drug to tubulin increases fluorescence intensity, causes a small emission blue shift, and has a quantum yield of 0.037.", + "Fluorescence increases as a function of drug concentration, with a high affinity site and an undetermined number of lower affinity sites.", + "Photolabeling, by exciting the fluorescent drug-tubulin complex at the absorption maximum of anthranilate, yields a covalent adduct confined to beta-tubulin.", + "Its formation is specific in that it is blocked by maytansine or vinblastine.", + "Tryptic hydrolysis identifies a single fluorescent beta-peptide coinciding with residues 175-213.", + "The interactions between various ligands at this central portion of beta-tubulin are discussed.", + "Amino Acid Sequence\nAnimals\nBinding Sites\nBrain\nChromatography, High Pressure Liquid\nCysteine\nKinetics\nMacromolecular Substances\nPeptide Fragments\nProtein Conformation\nRats\nSpectrometry, Fluorescence\nSpectrophotometry\nTrypsin\nTubulin\nVinblastine\northo-Aminobenzoates" + ], + "sentences": [ + "id: BE0001408; name: Tubulin beta-4A chain; organism: Humans; known_action: unknown; parent_key: DB01873.", + "id: BE0001367; name: Tubulin beta-4B chain; organism: Humans; known_action: unknown; parent_key: DB03010.", + "id: BE0004789; name: Tubulin beta-2 chain; organism: Pig roundworm; known_action: yes; position: 1; parent_key: DB00518.", + "id: BE0000710; name: High affinity immunoglobulin gamma Fc receptor I; organism: Humans; known_action: unknown; position: 9; parent_key: DB00111.", + "id: BE0000026; name: Tubulin beta-1 chain; organism: Humans; known_action: unknown; parent_key: DB06042.", + "id: BE0001039; name: High affinity nerve growth factor receptor; organism: Humans; known_action: unknown; position: 4; parent_key: DB00619.", + "id: BE0000143; name: Tubulin beta chain; organism: Humans; known_action: unknown; parent_key: DB01873.", + "id: BE0001039; name: High affinity nerve growth factor receptor; organism: Humans; known_action: unknown; position: 226; parent_key: DB12010.", + "id: BE0003134; name: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A; organism: Humans; known_action: unknown; parent_key: DB03597.", + "id: BE0001415; name: Tubulin beta-3 chain; organism: Humans; known_action: unknown; position: 34; parent_key: DB12695.", + "id: BE0001367; name: Tubulin beta-4B chain; organism: Humans; known_action: unknown; position: 35; parent_key: DB12695.", + "id: BE0000469; name: ATP-binding cassette sub-family C member 9; organism: Humans; known_action: unknown; parent_key: DB00171.", + "id: BE0000143; name: Tubulin beta chain; organism: Humans; known_action: unknown; parent_key: DB05147.", + "id: BE0004378; name: Disulfide bond formation protein B; organism: Escherichia coli (strain K12); known_action: unknown; position: 19; parent_key: DB08690.", + "id: BE0000710; name: High affinity immunoglobulin gamma Fc receptor I; organism: Humans; known_action: unknown; parent_key: DB00056.", + "id: BE0001408; name: Tubulin beta-4A chain; organism: Humans; known_action: unknown; parent_key: DB06042.", + "id: BE0003401; name: Tubulin beta-2B chain; organism: Humans; known_action: unknown; position: 2; parent_key: DB07574.", + "id: BE0009186; name: Tubulin alpha chain; organism: Plasmodium falciparum (isolate K1 / Thailand); known_action: unknown; position: 104; parent_key: DB11638.", + "id: BE0003345; name: Bifunctional protein BirA; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04651.", + "id: BE0000076; name: SEC14-like protein 4; organism: Humans; known_action: unknown; parent_key: DB00163.", + "id: BE0003401; name: Tubulin beta-2B chain; organism: Humans; known_action: unknown; parent_key: DB05147.", + "id: BE0003400; name: Tubulin beta-2A chain; organism: Humans; known_action: unknown; parent_key: DB05147.", + "id: BE0003713; name: Tubulin gamma-1 chain; organism: Humans; known_action: yes; position: 4; parent_key: DB00570.", + "id: BE0001367; name: Tubulin beta-4B chain; organism: Humans; known_action: no; position: 3; parent_key: DB00518.", + "id: BE0000212; name: High affinity cationic amino acid transporter 1; organism: Humans; known_action: unknown; parent_key: DB00125.", + "id: BE0000710; name: High affinity immunoglobulin gamma Fc receptor I; organism: Humans; known_action: unknown; position: 4; parent_key: DB00108.", + "id: BE0004201; name: 30S ribosomal protein S15; organism: Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579); known_action: unknown; position: 7; parent_key: DB08185.", + "id: BE0001039; name: High affinity nerve growth factor receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB13926.", + "id: BE0000197; name: Sodium channel protein type 5 subunit alpha; organism: Humans; known_action: yes; position: 2; parent_key: DB01426.", + "id: BE0000537; name: Thyroxine-binding globulin; organism: Humans; known_action: unknown; position: 164; parent_key: DB09130.", + "id: BE0000015; name: High affinity immunoglobulin epsilon receptor subunit alpha; organism: Humans; known_action: unknown; parent_key: DB05797.", + "id: BE0000015; name: High affinity immunoglobulin epsilon receptor subunit alpha; organism: Humans; known_action: yes; parent_key: DB00043.", + "id: BE0000428; name: RAC-alpha serine/threonine-protein kinase; organism: Humans; known_action: unknown; parent_key: DB06641.", + "id: BE0001039; name: High affinity nerve growth factor receptor; organism: Humans; known_action: yes; position: 12; parent_key: DB08896.", + "id: BE0001415; name: Tubulin beta-3 chain; organism: Humans; known_action: unknown; parent_key: DB01873.", + "id: BE0001415; name: Tubulin beta-3 chain; organism: Humans; known_action: yes; parent_key: DB04845.", + "id: BE0003402; name: Tubulin beta-6 chain; organism: Humans; known_action: unknown; parent_key: DB05147.", + "id: BE0000143; name: Tubulin beta chain; organism: Humans; known_action: unknown; position: 69; parent_key: DB11638.", + "id: BE0000212; name: High affinity cationic amino acid transporter 1; organism: Humans; known_action: unknown; parent_key: DB00123.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB07084.", + "id: BE0000015; name: High affinity immunoglobulin epsilon receptor subunit alpha; organism: Humans; known_action: yes; parent_key: DB00895.", + "id: BE0000283; name: Tubulin beta chain; organism: Yeast; known_action: yes; position: 1; parent_key: DB00400.", + "id: BE0004627; name: ADP-ribosylation factor-like protein 5B; organism: Humans; known_action: unknown; parent_key: DB04315.", + "id: BE0000710; name: High affinity immunoglobulin gamma Fc receptor I; organism: Humans; known_action: unknown; position: 6; parent_key: DB00112.", + "id: BE0000143; name: Tubulin beta chain; organism: Humans; known_action: yes; position: 6; parent_key: DB11641.", + "id: BE0000143; name: Tubulin beta chain; organism: Humans; known_action: unknown; position: 1; parent_key: DB15534.", + "id: BE0000511; name: Receptor tyrosine-protein kinase erbB-2; organism: Humans; known_action: yes; parent_key: DB05773.", + "id: BE0003400; name: Tubulin beta-2A chain; organism: Humans; known_action: unknown; position: 33; parent_key: DB12695.", + "id: BE0000706; name: High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A; organism: Humans; known_action: unknown; position: 3; parent_key: DB07954.", + "id: BE0000710; name: High affinity immunoglobulin gamma Fc receptor I; organism: Humans; known_action: yes; position: 6; parent_key: DB06607." + ] + }, + { + "example_idx": 127, + "anchor_id": 10438385583973290709, + "positive_id": 17222949367202814264, + "join_paths": [ + [ + 2, + 10, + 0.298828125 + ], + [ + 2, + 4, + 0.296875 + ], + [ + 2, + 19, + 0.294921875 + ], + [ + 2, + 6, + 0.29296875 + ], + [ + 2, + 43, + 0.29296875 + ] + ], + "rows": [ + "Orphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug for many years.", + "Here we show that orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 +/- 0.7 microM.", + "The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration- and patch-clamp techniques on cultured superior colliculus neurones.", + "Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner.", + "The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM (n = 6).", + "Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 +/- 0.002 10(6) M-1S-1) whereas the offset rate was concentration-independent (Koff 0.230 +/- 0.004 S-1).", + "Calculation of the ratio Koff/Kon revealed an apparent Kd-value of 17.2 microM which is nearly identical to the IC50 calculated at equilibrium.", + "Aged\nBinding, Competitive\nCerebral Cortex\nDizocilpine Maleate\nElectrophysiology\nExcitatory Amino Acid Antagonists\nFemale\nHumans\nIn Vitro Techniques\nIon Channel Gating\nMale\nMembranes\nMiddle Aged\nMuscarinic Antagonists\nNeurons\nOrphenadrine\nPatch-Clamp Techniques\nReceptors, N-Methyl-D-Aspartate\nReceptors, Phencyclidine\nSuperior Colliculi" + ], + "sentences": [ + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 1; parent_key: DB15489.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB00370.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 3; parent_key: DB00546.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 8; parent_key: DB01175.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB11823.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 14; parent_key: DB00477.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: yes; position: 14; parent_key: DB00193.", + "id: BE0001312; name: Tyrosine-protein kinase ZAP-70; organism: Humans; known_action: unknown; parent_key: DB02010.", + "id: BE0004723; name: Potassium voltage-gated channel subfamily C member 1; organism: Humans; known_action: yes; position: 11; parent_key: DB06637.", + "id: BE0000071; name: Peroxisome proliferator-activated receptor alpha; organism: Humans; known_action: unknown; position: 22; parent_key: DB00313.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 11; parent_key: DB06738.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: no; position: 7; parent_key: DB00934.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB00697.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 2; parent_key: DB00628.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 2; parent_key: DB13335.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09203.", + "id: BE0004852; name: Glutamate (NMDA) receptor; organism: Humans; known_action: no; position: 4; parent_key: DB13146.", + "id: BE0000924; name: Adenosine receptor A2a; organism: Humans; known_action: yes; position: 10; parent_key: DB00201.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB11477.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 10; parent_key: DB00843.", + "id: BE0000884; name: Excitatory amino acid transporter 2; organism: Humans; known_action: unknown; position: 22; parent_key: DB00142.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 4; parent_key: DB00186.", + "id: BE0003663; name: Alpha-1-acid glycoprotein 2; organism: Humans; known_action: unknown; position: 106; parent_key: DB14487.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 4; parent_key: DB00404.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 9; parent_key: DB01544.", + "id: BE0001054; name: Excitatory amino acid transporter 3; organism: Humans; known_action: unknown; parent_key: DB00128.", + "id: BE0009847; name: Voltage-gated Potassium Channels; known_action: unknown; position: 17; parent_key: DB01110.", + "id: BE0004077; name: Cyclin-dependent kinase 16; organism: Humans; known_action: unknown; position: 2; parent_key: DB07766.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 5; parent_key: DB00842.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 6; parent_key: DB09166.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 2; parent_key: DB01553.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 3; parent_key: DB00897.", + "id: BE0002341; name: Neuronal acetylcholine receptor subunit alpha-7; organism: Humans; known_action: yes; position: 2; parent_key: DB00674.", + "id: BE0004852; name: Glutamate (NMDA) receptor; organism: Humans; known_action: unknown; position: 41; parent_key: DB01238.", + "id: BE0009027; name: Heat shock 70 kDa protein 4; organism: Humans; known_action: unknown; position: 11; parent_key: DB12695.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 1; parent_key: DB09304.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: yes; position: 2; parent_key: DB00333.", + "id: BE0004077; name: Cyclin-dependent kinase 16; organism: Humans; known_action: unknown; position: 238; parent_key: DB12010.", + "id: BE0002212; name: Cyclin-dependent kinase 6; organism: Humans; known_action: yes; position: 2; parent_key: DB11730.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 2; parent_key: DB01511.", + "id: BE0000197; name: Sodium channel protein type 5 subunit alpha; organism: Humans; known_action: unknown; parent_key: DB01035.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 16; parent_key: DB01224.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 5; parent_key: DB13025.", + "id: BE0004956; name: NMDA receptor; organism: Humans; known_action: unknown; position: 14; parent_key: DB00312.", + "id: BE0000369; name: Vascular endothelial growth factor receptor 2; organism: Humans; known_action: yes; position: 1; parent_key: DB05578.", + "id: BE0004889; name: D(1) dopamine receptor; organism: Humans; known_action: unknown; position: 16; parent_key: DB00715.", + "id: BE0004852; name: Glutamate (NMDA) receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB09409.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB06678.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 2; parent_key: DB01594.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB00433." + ] + }, + { + "example_idx": 128, + "anchor_id": 16219576325891474631, + "positive_id": 7878599645967865389, + "join_paths": [ + [ + 8, + 36, + 0.359375 + ], + [ + 6, + 24, + 0.34765625 + ], + [ + 6, + 49, + 0.33984375 + ], + [ + 8, + 24, + 0.330078125 + ], + [ + 6, + 33, + 0.328125 + ] + ], + "rows": [ + "Dorzolamide hydrochloride (S,S-5,6-dihydro-4H-4-ethylamino-6-methylthieno [2,3-b]thiopyran-2-sulfonamide-7,7-dioxide HCl; MK-507; L-671,152) is a water-soluble, potent inhibitor of human carbonic anhydrase isoenzymes II and IV in vitro, the respective IC50 values being 0.18 nM and 6.9 nM.", + "In contrast, it was found to be a much weaker inhibitor of human carbonic anhydrase isoenzyme I (IC50 value of 600 nM).", + "The topical administration of one 50 microliters drop of 0.5%, 1% and 2% solutions of dorzolamide maximally lowered the intraocular pressure (IOP) of glaucomatous monkeys by 22%, 30% and 37%, respectively.", + "Good ocular hypotensive activity was also observed in ocular normotensive and hypertensive rabbits.", + "Its site of action was within the eye, and the reductions in IOP in both species was achieved via decreased aqueous humor inflow.", + "The duration of action of 2% dorzolamide was shorter than that of 0.5% timolol in glaucomatous monkeys.", + "The IOP lowering activity of timolol in this paradigm was enhanced by the concomitant instillation of dorzolamide.", + "Both acutely and repeatedly administered 2% dorzolamide did not decrease regional ocular blood flow in the rabbit, and the topical instillation of the drug had no adverse effects on the eye of rabbits, dogs and monkeys.", + "Dorzolamide has been approved in a number of countries for use in patients with ocular hypertension or open-angle glaucoma.", + "Administration, Topical\nAnimals\nCarbonic Anhydrase Inhibitors\nDogs\nDrug Combinations\nDrug Evaluation, Preclinical\nGlaucoma\nIntraocular Pressure\nMacaca\nOphthalmic Solutions\nRabbits\nSulfonamides\nThiophenes\nTimolol" + ], + "sentences": [ + "name: Esika Pro Compact High Definintion and Double Finish SPF 15 MEDIUM 1 - BEIGE; ingredients: Octinoxate + Titanium dioxide + Zinc oxide; parent_key: DB09321.", + "name: foundcealer multi-tasking foundation Broad Spectrum SPF 20 Sunscreen 54H deep honey; ingredients: Titanium dioxide + Zinc oxide; parent_key: DB09321.", + "name: Darzalex Faspro; ingredients: Daratumumab + Hyaluronidase (human recombinant); parent_key: DB09331.", + "name: Mint-latanoprost/timolol; ingredients: Latanoprost + Timolol; parent_key: DB00373.", + "name: Act Latanoprost/timolol; ingredients: Latanoprost + Timolol; parent_key: DB00654.", + "name: Timolol GFS; ingredients: Timolol; parent_key: DB00373.", + "name: Jamp-dorzolamide; ingredients: Dorzolamide; parent_key: DB00869.", + "name: Dorzolamide HCl and Timolol Maleate; ingredients: Dorzolamide + Timolol; parent_key: DB00373.", + "name: Timoptic; ingredients: Timolol; parent_key: DB00373.", + "name: Istalol; ingredients: Timolol; parent_key: DB00373.", + "name: Tim-Brim-Dor-Lat; ingredients: Brimonidine + Dorzolamide + Latanoprost + Timolol; parent_key: DB00869.", + "name: Dorzolamide Hydrochloride-timolol Maleate; ingredients: Dorzolamide + Timolol; parent_key: DB00373.", + "name: Apo-latanoprost-timop; ingredients: Latanoprost + Timolol; parent_key: DB00373.", + "name: Rhoxal-timolol 0.25%; ingredients: Timolol; parent_key: DB00373.", + "name: Dorzolamide hydrochloride; ingredients: Dorzolamide; parent_key: DB00869.", + "name: 4253 First Aid Kit; ingredients: Bacitracin + Benzalkonium + Ethanol + Lidocaine + Lidocaine + Neomycin + Polymyxin B + Povidone-iodine + Water; parent_key: DB00626.", + "name: PMS-dorzolamide-timolol; ingredients: Dorzolamide + Timolol; parent_key: DB00869.", + "name: Blocadren Tab 10mg; ingredients: Timolol; parent_key: DB00373.", + "name: Timolol Solution - 0.25%; ingredients: Timolol; parent_key: DB00373.", + "name: Protropin Inj Pws 10mg/vial; ingredients: Somatrem + Water; parent_key: DB09145.", + "name: HAEGARDA C1 Esterase Inhibitor Subcutaneous (Human); ingredients: Human C1-esterase inhibitor; parent_key: DB06404.", + "name: Dorzolamide; ingredients: Dorzolamide; parent_key: DB00869.", + "name: Novo-timol Liq 0.25%; ingredients: Timolol; parent_key: DB00373.", + "name: Tim-Dor-Lat; ingredients: Dorzolamide + Latanoprost + Timolol; parent_key: DB00654.", + "name: Dorzolamide Hydrochloride and Timolol Maleate ophthalmic Solution; ingredients: Dorzolamide + Timolol; parent_key: DB00869.", + "name: 4267 First Aid Kit; ingredients: Acetaminophen + Ammonia + Benzalkonium + Ethanol + Isopropyl alcohol + Lidocaine + Neomycin + Water; parent_key: DB00281.", + "name: Med-dorzolamide-timolol; ingredients: Dorzolamide + Timolol; parent_key: DB00869.", + "name: Tim-Brim-Dor PF; ingredients: Brimonidine + Dorzolamide + Timolol; parent_key: DB00869.", + "name: Sooryehan Dabityoon Jiyoon Cover Makeup 21; ingredients: Octinoxate + Titanium dioxide; parent_key: DB09496.", + "name: Med Timolol Liq Oph 0.25%; ingredients: Timolol; parent_key: DB00373.", + "name: Cosopt PF; ingredients: Dorzolamide + Timolol; parent_key: DB00373.", + "name: Betimol; ingredients: Timolol; parent_key: DB00373.", + "name: Blocadren; ingredients: Timolol; parent_key: DB00373.", + "name: Dorzolamide Hydrochloride-Timolol Maleate; ingredients: Dorzolamide + Timolol; parent_key: DB00869.", + "name: Dorzolamide Hydrochloride and Timolol Maleate; ingredients: Dorzolamide + Timolol; parent_key: DB00373.", + "name: Berinert; ingredients: Human C1-esterase inhibitor; parent_key: DB06404.", + "name: Dorzolamide Hydrochloride Ophthalmic Solution; ingredients: Dorzolamide; parent_key: DB00869.", + "name: bareMinerals Skinlongevity Vital Power Moisturizer Broad Spectrum SPF 30; ingredients: Titanium dioxide + Zinc oxide; parent_key: DB09321.", + "name: Timolol Maleate; ingredients: Timolol; parent_key: DB00373.", + "name: Tim-Brim-Dor-Lat; ingredients: Brimonidine + Dorzolamide + Latanoprost + Timolol; parent_key: DB00654.", + "name: Tim-Dor-Lat; ingredients: Dorzolamide + Latanoprost + Timolol; parent_key: DB00869.", + "name: 4216 First Aid Kit; ingredients: Acetylsalicylic acid + Ammonia + Bacitracin + Benzalkonium + Lidocaine + Neomycin + Polymyxin B + Water; parent_key: DB00626.", + "name: Apo-dorzo-timop; ingredients: Dorzolamide + Timolol; parent_key: DB00869.", + "name: Rabbit; ingredients: Rabbit; parent_key: DB10415.", + "name: Nu-timolol Tab 20mg; ingredients: Timolol; parent_key: DB00373.", + "name: Cosopt PF; ingredients: Dorzolamide + Timolol; parent_key: DB00869.", + "name: Ratio-timolol Maleate 0.25%; ingredients: Timolol; parent_key: DB00373.", + "name: Tim-Dor PF; ingredients: Dorzolamide + Timolol; parent_key: DB00373.", + "name: Super Origin Cc Spf30 Pa Plus Plus Tinted; ingredients: Octinoxate + Octisalate + Titanium dioxide; parent_key: DB09496.", + "name: Dorzolamide and Timolol; ingredients: Dorzolamide + Timolol; parent_key: DB00869." + ] + }, + { + "example_idx": 129, + "anchor_id": 6088671476029953583, + "positive_id": 13730122248912998424, + "join_paths": [ + [ + 0, + 22, + 0.2197265625 + ], + [ + 0, + 25, + 0.2197265625 + ], + [ + 1, + 25, + 0.2158203125 + ], + [ + 3, + 25, + 0.205078125 + ], + [ + 2, + 25, + 0.203125 + ] + ], + "rows": [ + "Fluoxetine (Prozac) inhibited the membrane currents elicited by serotonin (5-hydroxytryptamine; 5HT) in Xenopus oocytes expressing either cloned 5HT2C receptors or 5HT receptors encoded by rat cortex mRNA.", + "Responses of 5HT2C receptors, elicited by nM concentrations of 5HT, were rapidly and reversibly blocked by micromolar concentrations of fluoxetine.", + "For responses elicited by 1 microM 5HT, the IC50 of fluoxetine inhibition was approximately 20 microM.", + "In accord with the electrophysiological results, fluoxetine inhibited the binding of [3H]5HT to 5HT2C receptors expressed in HeLa cells (Ki approximately 65-97 nM), and the binding to 5HT receptors in rat cortex membranes was also inhibited but less efficiently (Ki approximately 56 microM).", + "Our results show that fluoxetine is a competitive and reversible antagonist of 5HT2C receptors and suggest that some therapeutic effects of fluoxetine may involve blockage of 5HT receptors, in addition to its known blockage of 5HT transporters.", + "Similar work may help to design more selective compounds for use in the treatment of brain disorders.", + "Angiotensin III\nAnimals\nBinding, Competitive\nBrain\nCarrier Proteins\nDose-Response Relationship, Drug\nFluoxetine\nGene Expression\nHeLa Cells\nHumans\nMembrane Glycoproteins\nMembrane Transport Proteins\nNerve Tissue Proteins\nOocytes\nPatch-Clamp Techniques\nProtein Binding\nRNA, Messenger\nRats\nReceptor, Serotonin, 5-HT2C\nReceptors, Serotonin\nSerotonin\nSerotonin Plasma Membrane Transport Proteins\nSerotonin Uptake Inhibitors\nTransfection\nXenopus" + ], + "sentences": [ + "id: BE0002468; name: Voltage-dependent anion-selective channel protein 1; organism: Humans; known_action: unknown; position: 39; parent_key: DB14009.", + "id: BE0009972; name: Plasma membrane calcium-transporting ATPase; organism: Humans; known_action: yes; position: 20; parent_key: DB01159.", + "id: BE0009793; name: Kainate receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB00273.", + "id: BE0000436; name: cGMP-inhibited 3',5'-cyclic phosphodiesterase A; organism: Humans; known_action: yes; parent_key: DB01166.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 13; parent_key: DB09167.", + "id: BE0004179; name: Outer membrane protein II; organism: Neisseria meningitidis; known_action: unknown; position: 37; parent_key: DB04147.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 10; parent_key: DB08922.", + "id: BE0000956; name: Nuclear receptor subfamily 1 group I member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB13952.", + "id: BE0000770; name: Mu-type opioid receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB09089.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: no; position: 3; parent_key: DB00245.", + "id: BE0003980; name: Probable outer membrane protein; organism: Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228); known_action: unknown; position: 16; parent_key: DB04233.", + "id: BE0002833; name: Copper transport protein ATOX1; organism: Humans; known_action: unknown; parent_key: DB03127.", + "id: BE0003394; name: Brain-derived neurotrophic factor; organism: Humans; known_action: unknown; parent_key: DB05047.", + "id: BE0009630; name: Excretory Secretory (ES) proteins; organism: Fasciola hepatica; known_action: unknown; position: 3; parent_key: DB12245.", + "id: BE0009719; name: Glucocorticoid binding proteins; organism: Humans; known_action: unknown; position: 2; parent_key: DB06718.", + "id: BE0003708; name: 30S ribosomal protein S14; organism: Escherichia coli (strain K12); known_action: yes; position: 2; parent_key: DB00759.", + "id: BE0001288; name: Triggering receptor expressed on myeloid cells 1; organism: Humans; known_action: unknown; parent_key: DB01694.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; position: 1; parent_key: DB01114.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 2; parent_key: DB00191.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: unknown; position: 5; parent_key: DB00193.", + "id: BE0009755; name: Rabies Virus Proteins; organism: Rabies virus (strain Pasteur vaccins / PV); known_action: yes; position: 1; parent_key: DB11603.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 5; parent_key: DB13025.", + "id: BE0004862; name: Serotonin Receptors; organism: Humans; known_action: unknown; position: 13; parent_key: DB00715.", + "id: BE0001223; name: cGMP-inhibited 3',5'-cyclic phosphodiesterase B; organism: Humans; known_action: unknown; parent_key: DB01640.", + "id: BE0000436; name: cGMP-inhibited 3',5'-cyclic phosphodiesterase A; organism: Humans; known_action: yes; parent_key: DB00261.", + "id: BE0005582; name: 5HT3 serotonin receptor; organism: Humans; known_action: unknown; position: 3; parent_key: DB09207.", + "id: BE0000393; name: 5-hydroxytryptamine receptor 2B; organism: Humans; known_action: unknown; position: 4; parent_key: DB01454.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 2; parent_key: DB00543.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: yes; position: 1; parent_key: DB11477.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 4; parent_key: DB00370.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 14; parent_key: DB00477.", + "id: BE0000332; name: Enoyl-[acyl-carrier-protein] reductase [NADH]; organism: Mycobacterium tuberculosis; known_action: unknown; position: 2; parent_key: DB08604.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 2; parent_key: DB09194.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: unknown; position: 6; parent_key: DB09068.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 2; parent_key: DB00321.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 3; parent_key: DB00193.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB09195.", + "id: BE0009463; name: Mitogen-activated protein kinase kinase kinase 11; organism: Humans; known_action: unknown; position: 178; parent_key: DB12010.", + "id: BE0000576; name: Penicillin-binding protein 1A; organism: Clostridium perfringens (strain 13 / Type A); known_action: yes; parent_key: DB01061.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; parent_key: DB00726.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: yes; position: 3; parent_key: DB09204.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 4; parent_key: DB01142.", + "id: BE0004863; name: Alpha-1 adrenergic receptors; organism: Humans; known_action: unknown; position: 17; parent_key: DB00543.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 1; parent_key: DB00215.", + "id: BE0000436; name: cGMP-inhibited 3',5'-cyclic phosphodiesterase A; organism: Humans; known_action: yes; position: 1; parent_key: DB01223.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; parent_key: DB05964.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: unknown; parent_key: DB05422.", + "id: BE0004864; name: Alpha-2 adrenergic receptors; organism: Humans; known_action: unknown; position: 23; parent_key: DB00543.", + "id: BE0000588; name: Penicillin-binding protein 1A; organism: Escherichia coli (strain K12); known_action: yes; position: 5; parent_key: DB00274.", + "id: BE0000749; name: Sodium-dependent serotonin transporter; organism: Humans; known_action: yes; position: 3; parent_key: DB00579." + ] + }, + { + "example_idx": 130, + "anchor_id": 14007336842325753298, + "positive_id": 7502606472422468628, + "join_paths": [ + [ + 0, + 23, + 0.255859375 + ], + [ + 0, + 24, + 0.255859375 + ], + [ + 0, + 27, + 0.25390625 + ], + [ + 0, + 41, + 0.25 + ], + [ + 0, + 48, + 0.25 + ] + ], + "rows": [ + "BACKGROUND: Retinoid research in the field of dermatology has been influenced by the clinical success of topical tretinoin and oral isotretinoin in the treatment of acne, and by the discovery of high-affinity binding proteins for retinoic acid mediating its action and interaction with other vitamins and hormones.", + "OBJECTIVE: We sought molecules with an optimal balance between stability, efficacy, and local tolerance for topical acne therapy.", + "METHODS: In vitro and in vivo bioassay systems were used to test the ability of retinoids to modulate cell proliferation and differentiation.", + "In addition, antiinflammatory properties were assessed.", + "Binding and transactivation assays were used to compare affinities and transcriptional activities of adapalene and tretinoin for the nuclear transcription factors, retinoic acid receptors (RARs).", + "RESULTS AND CONCLUSION: Adapalene is a stable naphthoic acid derivative with potent retinoid pharmacology, controlling cell proliferation and differentiation.", + "In addition it has significant antiinflammatory action.", + "The nuclear gene transcription factors RAR beta and RAR gamma mediate the retinoid activity of adapalene.", + "Adapalene\nAdministration, Topical\nAnimals\nAnti-Inflammatory Agents, Non-Steroidal\nCell Differentiation\nCell Division\nCells, Cultured\nGene Expression\nHeLa Cells\nHumans\nNaphthalenes\nSignal Transduction\nSkin" + ], + "sentences": [ + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; position: 3; parent_key: DB00755.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; position: 2; parent_key: DB00210.", + "id: BE0001412; name: Cell division protein ZipA homolog; organism: Shigella flexneri; known_action: unknown; parent_key: DB04154.", + "id: BE0000385; name: Interferon alpha/beta receptor 2; organism: Humans; known_action: yes; parent_key: DB00034.", + "id: BE0004878; name: Nuclear factor of activated T-cells, cytoplasmic 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00852.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; parent_key: DB00799.", + "id: BE0004000; name: Cell division protein ZipA; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB02191.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; position: 5; parent_key: DB00523.", + "id: BE0009400; name: Non-receptor tyrosine-protein kinase TNK1; organism: Humans; known_action: unknown; position: 43; parent_key: DB12010.", + "id: BE0009366; name: Alveolar cells; organism: Humans; known_action: unknown; position: 2; parent_key: DB11588.", + "id: BE0000215; name: Peroxisome proliferator-activated receptor gamma; organism: Humans; known_action: unknown; position: 2; parent_key: DB00912.", + "id: BE0000663; name: Retinoic acid receptor alpha; organism: Humans; known_action: yes; parent_key: DB04942.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: unknown; parent_key: DB05467.", + "id: BE0009352; name: Lung epithelial cells; organism: Humans; known_action: yes; position: 1; parent_key: DB11332.", + "id: BE0000764; name: Gamma-aminobutyric acid receptor subunit alpha-6; organism: Humans; known_action: yes; position: 6; parent_key: DB00312.", + "id: BE0000663; name: Retinoic acid receptor alpha; organism: Humans; known_action: yes; position: 2; parent_key: DB00459.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: unknown; parent_key: DB05785.", + "id: BE0000172; name: Beta-1 adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB00571.", + "id: BE0009373; name: Skin epithelial cells; organism: Humans; known_action: yes; position: 1; parent_key: DB11112.", + "id: BE0001380; name: Cell division protein FtsZ; organism: Mycobacterium tuberculosis; known_action: unknown; parent_key: DB04315.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; position: 4; parent_key: DB00459.", + "id: BE0003244; name: Endo-1,4-beta-xylanase A; organism: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099); known_action: unknown; parent_key: DB02379.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: unknown; position: 1; parent_key: DB07294.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: unknown; position: 11; parent_key: DB00755.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: yes; parent_key: DB04942.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: unknown; parent_key: DB02258.", + "id: BE0009979; name: Hematopoietic stem cells; organism: Humans; known_action: unknown; position: 1; parent_key: DB03843.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: yes; position: 3; parent_key: DB00926.", + "id: BE0000860; name: Receptor activity-modifying protein 2; organism: Humans; known_action: yes; position: 3; parent_key: DB01278.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: unknown; parent_key: DB02741.", + "id: BE0001412; name: Cell division protein ZipA homolog; organism: Shigella flexneri; known_action: unknown; parent_key: DB03916.", + "id: BE0009149; name: Retinoid isomerohydrolase; organism: Humans; known_action: yes; position: 1; parent_key: DB13932.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; position: 6; parent_key: DB00926.", + "id: BE0001412; name: Cell division protein ZipA homolog; organism: Shigella flexneri; known_action: unknown; parent_key: DB01967.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: unknown; parent_key: DB03279.", + "id: BE0000861; name: Receptor activity-modifying protein 3; organism: Humans; known_action: yes; position: 4; parent_key: DB01278.", + "id: BE0000694; name: Beta-2 adrenergic receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB09080.", + "id: BE0000859; name: Receptor activity-modifying protein 1; organism: Humans; known_action: yes; position: 2; parent_key: DB01278.", + "id: BE0000144; name: Retinoic acid receptor gamma; organism: Humans; known_action: yes; position: 1; parent_key: DB12808.", + "id: BE0003211; name: N-acylamino acid racemase; organism: Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / LMG 4051 / NBRC 15346 / NCIMB 9279 / R1 / VKM B-1422); known_action: unknown; parent_key: DB04167.", + "id: BE0004000; name: Cell division protein ZipA; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB03916.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: unknown; parent_key: DB02877.", + "id: BE0009209; name: Tubulin beta chain; organism: Plasmodium falciparum (isolate 3D7); known_action: unknown; position: 127; parent_key: DB11638.", + "id: BE0009373; name: Skin epithelial cells; organism: Humans; known_action: yes; position: 1; parent_key: DB11185.", + "id: BE0004000; name: Cell division protein ZipA; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB01967.", + "id: BE0001827; name: Cell division control protein 2 homolog; organism: Plasmodium falciparum (isolate K1 / Thailand); known_action: unknown; parent_key: DB02733.", + "id: BE0009352; name: Lung epithelial cells; organism: Humans; known_action: unknown; position: 9; parent_key: DB14001.", + "id: BE0004000; name: Cell division protein ZipA; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB04154.", + "id: BE0000206; name: Retinoic acid receptor beta; organism: Humans; known_action: yes; position: 1; parent_key: DB00210.", + "id: BE0001102; name: Prostatic acid phosphatase; organism: Humans; known_action: yes; parent_key: DB06688." + ] + }, + { + "example_idx": 131, + "anchor_id": 9840657151168647282, + "positive_id": 13621217315622312832, + "join_paths": [ + [ + 0, + 38, + 0.158203125 + ], + [ + 0, + 15, + 0.1572265625 + ] + ], + "rows": [ + "In this review the clinical pharmacology of HIV protease inhibitors, a new class of antiretroviral drugs, is discussed.", + "After considering HIV protease function and structure, the development of inhibitors of HIV protease is presented.", + "Three protease inhibitors are reviewed in more detail: saquinavir, indinavir, and ritonavir.", + "Clinical trial results with these agents are evaluated.", + "Furthermore, adverse effects, resistance, dosage and administration, clinical pharmacokinetics, pharmacokinetic-pharmacodynamic relationships, and drug interactions are discussed.", + "Acquired Immunodeficiency Syndrome\nClinical Trials as Topic\nHIV Protease\nHIV Protease Inhibitors\nHumans\nIndinavir\nRitonavir\nSaquinavir" + ], + "sentences": [ + "ref-id: L13859; 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parent_key: DB09338.", + "ref-id: L1534; title: PEGylation of a Factor VIII–Phosphatidylinositol Complex: Pharmacokinetics and Immunogenicity in Hemophilia A Mice; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291190/; parent_key: DB09329.", + "ref-id: L13841; title: Deciphera phase 1 study results; url: https://www.deciphera.com/wp-content/uploads/2018/10/ESMO-2018-George-et-al.-for-submission-to-ESMO-final.pdf; parent_key: DB14840.", + "ref-id: L5798; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT01123486; parent_key: DB00327.", + "ref-id: L2009; title: Vinorelbine FDA pharmacology review; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-388S008_Navelbine_biopharmr.pdf; parent_key: DB00361.", + "ref-id: L14375; title: INOVIO Press release phase 1/2 clinical trial; url: http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIO-and-IVI-Partner-with-Seoul-National-University-Hospital-to-Start-Phase-12-Clinical-Trial-of-INOVIOs-COVID-19-DNA-Vaccine-INO-4800-in-South-Korea/default.aspx; 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title: Clinical pharmacology review of opicapone for the treatment of Parkinson's disease; url: https://www.futuremedicine.com/doi/10.2217/nmt-2016-0022; parent_key: DB11632.", + "ref-id: L8983; title: FDA Approved Drug Products: Vogelxo Testosterone Gel; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204399s000lbl.pdf; parent_key: DB00624.", + "ref-id: L4835; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02456883; parent_key: DB12141.", + "ref-id: L1168; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/record/NCT02612298?view=results; parent_key: DB09204.", + "ref-id: L6205; title: WHO Model List of Essential Medicines 19th List (April 2015 - Amended November 2015); url: https://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1; parent_key: DB00581.", + "ref-id: L12177; title: NIH: Clinical Trial NCT04257656; url: https://clinicaltrials.gov/ct2/show/NCT04257656; parent_key: DB14761.", + "ref-id: L6511; title: Ketorolac: A Reappraisal of its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use In Pain Management; url: https://link.springer.com/article/10.2165/00003495-199753010-00012; parent_key: DB00465.", + "ref-id: L1377; title: Clinical Pharmacology of Antianginal Drugs; url: https://books.google.ca/books?id=nuXrCAAAQBAJ&pg=PA366&lpg=PA366&dq=molsidomine+liver+metabolism&source=bl&ots=qBCXm0vm5D&sig=lxa3AYTHHhiqJe-_8X94eUCSW_0&hl=en&sa=X&ved=0ahUKEwiXzM7rz7fZAhUD5mMKHcS0AmMQ6AEIczAJ#v=onepage&q=esterase&f=false; parent_key: DB09282.", + "ref-id: L10914; title: Upadacitinib Clinical Pharmacology and Biopharmaceutics Review(s) - FDA; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211675Orig1s000ClinPharmR.pdf; parent_key: DB15091.", + "ref-id: L2169; title: Influence of Lifestyle Factors on Breast Cancer Risk; url: https://www.karger.com/Article/Abstract/369571; parent_key: DB11239.", + "ref-id: L1136; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/results/NCT02411929?sect=Xgf0156#outcome10; 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parent_key: DB09299.", + "ref-id: L1707; title: Radiographic constrat agents; url: https://www.ranzcr.com/documents/593-notes-on-radiographic-contrast-rad-part-i-exam-ait/file; parent_key: DB09347.", + "ref-id: L12042; title: BioCryst Initiates Phase 1 Clinical Trial of Galidesivir; url: http://ir.biocryst.com/news-releases/news-release-details/biocryst-initiates-phase-1-clinical-trial-galidesivir; parent_key: DB11676.", + "ref-id: L14372; title: INO-4800 Phase I clinical trial NCT04336410; url: https://clinicaltrials.gov/ct2/show/NCT04336410; parent_key: DB15693.", + "ref-id: L8192; title: Pharmacology review, FDA; url: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204820Orig1s000PharmR.pdf; parent_key: DB01394.", + "ref-id: L4834; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT02181660; parent_key: DB12141.", + "ref-id: L5314; title: Clinical trials; url: https://clinicaltrials.gov/ct2/show/NCT03172208; parent_key: DB06081.", + "ref-id: L1501; title: Neurobiological Basis of Response to Vayarin in Adults With ADHD: an fMRI Study of Brain Activation Pre and Post Treatment (VAYA-fMRI); url: https://clinicaltrials.gov/ct2/show/NCT02473419; parent_key: DB09328.", + "ref-id: L7126; title: Clinical Trials: BOSTON Trial; url: https://clinicaltrials.gov/ct2/show/NCT03110562; parent_key: DB11942.", + "ref-id: L1215; title: Clinical Trial NCT00299897; url: https://www.clinicaltrials.gov/ct2/show/NCT00299897; parent_key: DB00721.", + "ref-id: L12675; title: Chinese Clinical Trial Register: A phase I clinical trial for recombinant novel coronavirus (2019-COV) vaccine (adenoviral vector); url: http://www.chictr.org.cn/showprojen.aspx?proj=51154; parent_key: DB15655.", + "ref-id: L1898; title: Pyrantel Dosage; url: https://www.drugs.com/dosage/pyrantel.html; parent_key: DB11156." + ] + }, + { + "example_idx": 132, + "anchor_id": 5510157834932725959, + "positive_id": 15842948492935639167, + "join_paths": [ + [ + 0, + 15, + 0.392578125 + ], + [ + 3, + 15, + 0.37109375 + ], + [ + 1, + 15, + 0.3671875 + ], + [ + 0, + 20, + 0.36328125 + ], + [ + 3, + 20, + 0.36328125 + ] + ], + "rows": [ + "Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) of the 2,6-disubstituted naphthyl-alkanone class.", + "Nabumetone is metabolised to an active metabolite 6-methoxy-2-napthylacetic acid (6-MNA) which is a relatively selective cyclo-oxygenase-2 inhibitor that has anti-inflammatory and analgesic properties.", + "Nabumetone and its metabolites bind extensively to plasma albumin.", + "Nabumetone is eliminated following biotransformation to 6-MNA, which does not undergo enterohepatic circulation and the respective glucoroconjugated metabolites are excreted in urine.", + "Substantial concentrations of 6-MNA are attained in synovial fluid, which is he proposed site of action in chronic inflammatory arthropathies.", + "A smaller area under the plasma concentration-time curve (AUC) is evident at steady state as compared with a single dose; this is possibly due to an increase in the volume of distribution and saturation of protein binding.", + "Relationships between 6-MNA concentrations and the therapeutic and toxicological effects have yet to be elucidated for this NSAID.", + "Renal failure significantly reduces 6-MNA elimination but steady-state concentrations of 6-MNA are not increased, possibly because of nonlinear protein binding.", + "Elderly patients with osteoarthritis demonstrate decreased elimination and increased plasma concentrations of nabumetone as compared with young healthy volunteers.", + "Rheumatic disease activity also influences 6-MNA plasma concentrations, as patients with more active disease and lower serum albumin concentrations demonstrate a lower area under the plasma concentration versus time curve.", + "A reduced bioavailability of 6-MNA in patients with severe hepatic impairment is also evident.", + "Dosage adjustment may be required in the elderly, patients with active rheumatic disease and those with hepatic impairment, but not in patients with mild-to-moderate renal failure.", + "Anti-Inflammatory Agents, Non-Steroidal\nButanones\nCyclooxygenase Inhibitors\nDose-Response Relationship, Drug\nHumans\nIntestinal Absorption\nNabumetone\nProtein Binding\nSynovial Fluid\nTissue Distribution" + ], + "sentences": [ + "ref-id: L1390; title: Psychiatry: The State of the Art Volume 3 Pharmacopsychiatry; url: https://books.google.ca/books?id=IgraBwAAQBAJ&pg=PA209&lpg=PA209&dq=pirlindole+pharmacokinetics&source=bl&ots=lN64zZ3EEg&sig=UN0rzaFBQg_vqXbJHo2ls2BO2JA&hl=en&sa=X&ved=0ahUKEwj12av-kLjZAhVP0mMKHYXuCXYQ6AEIRzAE#v=onepage&q=pirlindole%20pharmacokinetics&f=false; parent_key: DB09244.", + "ref-id: L1158; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-enanthate/; parent_key: DB13944.", + "ref-id: L1152; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-cypionate/; parent_key: DB13943.", + "ref-id: L2183; title: Plasma Pharmacokinetics of Two Consecutive Doses of Ferumoxytol in Healthy Subjects; url: https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1038/clpt.2010.80; parent_key: DB06215.", + "ref-id: L1890; title: Imaging-related medications: a class overview; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014815/; parent_key: DB09313.", + "ref-id: L12831; title: FDA Approved Drug Products: Ceprotin (protein C concentration [human]) powder for solution; url: https://www.fda.gov/media/75033/download; parent_key: DB11312.", + "ref-id: L2100; title: Pharmacokinetics, tissue distribution, and excretion of zinc oxide nanoparticles; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394467/; parent_key: DB14487.", + "ref-id: L1670; title: Review of the toxicology, pharmacodynamics and pharmacokinetics of thiocolchicoside, a GABA-agonist muscle relaxant with anti-inflammatory and analgesic actions; url: https://www.researchgate.net/publication/291818675_Review_of_the_toxicology_pharmacodynamics_and_pharmacokinetics_of_thiocolchicoside_a_GABA-agonist_muscle_relaxant_with_anti-inflammatory_and_analgesic_actions; parent_key: DB11582.", + "ref-id: L1159; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-propionate/testosterone-propionate-cycle/; parent_key: DB01420.", + "ref-id: L1152; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-cypionate/; 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url: https://chem.nlm.nih.gov/chemidplus/rn/42924-53-8; parent_key: DB00461.", + "ref-id: L2965; title: Enhancement of Tumor Response to -Radiation by an Inhibitor of Cyclooxygenase-2 Enzyme; url: https://www.researchgate.net/publication/31132809_Enhancement_of_Tumor_Response_to_-Radiation_by_an_Inhibitor_of_Cyclooxygenase-2_Enzyme; parent_key: DB14059.", + "ref-id: L3104; title: PDR-Human Albumin; url: http://www.pdr.net/drug-summary/Human-Albumin-Grifols-25--albumin--human--1765; parent_key: DB00062.", + "ref-id: L7619; title: FDA Approved Drug Products: Misoprostol and Diclofenac Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020607s031lbl.pdf; parent_key: DB00929.", + "ref-id: L1383; title: Determination of azelnidipine by LC–ESI-MS and its application to a pharmacokinetic study in healthy Chinese volunteers; url: http://www.ingentaconnect.com/content/govi/pharmaz/2008/00000063/00000008/art00003?crawler=true; parent_key: DB09230.", + "ref-id: L6466; title: Nabumetone Health Canada Monograph; 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url: https://watermark.silverchair.com/jcem5830.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAaowggGmBgkqhkiG9w0BBwagggGXMIIBkwIBADCCAYwGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM8C4jETgsbOcKN1RJAgEQgIIBXby2TDMTqLoxgQ6ubmlN4HjHutX56ZK5YSit8uXY_SxCH-FeJHHRd96DO6Xelfs_AWHgOkwYiSjyYiuJ6R5G75IuAh7TqXiqfShWHfHPGcr6jbX8N95S0Q25p6CTV_9-3_c8L1bA6AmtrsINgJbKbocjEZYJz0Dw51NqiUsO8g8f8Junna_pmyfUuz8j4wEmV7mywP_MWfvtH85E-gZ1XvGsQ7CiBLVtSW2g_4VGxNQgySqQqOqwvwdBXWNGFaIdAEDcvTqNslGyKbBNDf9OG_vZdli5fQXImHAhuyg1MGK4DKqzXh1FLuaRnRpOILyQrw5Wdw9pmiH_t6LxvC4RDlG5gi_fhjlAbLBZSLFxxefkX9NV8s9_sjKTpGFpVRDLooh6_luWVvHcFmS8OyEbaj-Jy8E0d_n_JndMakMvJT1ijVQpi4RbOrA6zCGeAvlPoDhBVT5IfTTQ61uJSsQ; parent_key: DB08862.", + "ref-id: L3109; title: Human Albumin; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90f0c351-3977-2b84-0a6a-e9cb091430ca; parent_key: DB00062.", + "ref-id: L2678; title: Binding mechanism of triclocarban with human serum albumin: Effect on the conformation and activity of the model transport protein; url: https://www.sciencedirect.com/science/article/pii/S0167732217339946; parent_key: DB11155.", + "ref-id: L3102; title: ALBUMIN (HUMAN)- albumin human solution DailyMed; url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ddaae99-05e1-e05c-e63c-0c58965d157d; parent_key: DB00062.", + "ref-id: L5789; title: Using Acetaminophen and Nonsteroidal Anti-inflammatory Drugs Safely; url: https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingOver-the-CounterMedicines/SafeUseofOver-the-CounterPainRelieversandFeverReducers/ucm164977.htm; parent_key: DB00316.", + "ref-id: L1823; title: Wilson Disease; url: https://www.niddk.nih.gov/health-information/liver-disease/wilson-disease; parent_key: DB06778.", + "ref-id: L1161; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/testosterone-propionate/testosterone-propionate-dosage/; parent_key: DB01420.", + "ref-id: L1413; title: Tianeptine properties; url: http://datasheets.scbt.com/sds/aghs/en/sc-204345.pdf; parent_key: DB09289.", + "ref-id: L1713; title: Pharmacokinetics of amrubicin in lung cancer patients with impaired hepatic function; url: https://www.sciencedirect.com/science/article/pii/S2213089616300603; parent_key: DB06263.", + "ref-id: L2473; title: The pharmacokinetics of salicylate; url: https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.1980.tb01811.x; parent_key: DB11071.", + "ref-id: L6145; title: Clinicaltrails.gov: National Pregnancy Registry for Atypical Antipsychotics; url: https://clinicaltrials.gov/ct2/show/NCT01246765; parent_key: DB01238.", + "ref-id: L2100; title: Pharmacokinetics, tissue distribution, and excretion of zinc oxide nanoparticles; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394467/; parent_key: DB01593.", + "ref-id: L2672; title: FDA bans triclosan and triclocarban in consumer soaps; url: https://cen.acs.org/articles/94/web/2016/09/FDA-bans-triclosan-triclocarban-consumer.html; parent_key: DB11155.", + "ref-id: L12807; title: FDA Approved Products: Relafen (nabumetone) tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/019583s023lbl.pdf; parent_key: DB00461.", + "ref-id: L752; title: Magnesium Absorption in Humans ; url: http://e-collection.library.ethz.ch/eserv/eth:26387/eth-26387-02.pdf; parent_key: DB09409.", + "ref-id: L1234; title: Aspirin, Non-Aspirin Nonsteroidal Anti-inflammatory Drugs, or Acetaminophen and risk of ovarian cancer; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3454462/; parent_key: DB09212.", + "ref-id: L1697; title: Therapeutic effects of mifepristone combined with Gestrinone on patients with endometriosis; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103146/; parent_key: DB11619.", + "ref-id: L1228; title: Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks; url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036661/; parent_key: DB09212.", + "ref-id: L1164; title: Steroidal; url: https://www.steroidal.com/steroid-profiles/andriol/; parent_key: DB13946.", + "ref-id: L7985; title: FDA Approved Drug Products: Nebivolol Tablets; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf; parent_key: DB04861.", + "ref-id: L12687; title: Health Canada Product Monograph: NiaStase RT (eptacog alfa (activated) ) powder for injection; url: https://pdf.hres.ca/dpd_pm/00042076.PDF; parent_key: DB00036.", + "ref-id: L2932; title: Avatrombopag Gains FDA Approval for Patients with Chronic Liver Disease; url: https://www.specialtypharmacytimes.com/news/avatrombopag-gains-fda-approval-for-patients-with-chronic-liver-disease; parent_key: DB11995.", + "ref-id: L14165; title: FDA Approved Drug Products: Ingrezza (valbenazine) oral capsules; url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209241s016lbl.pdf; parent_key: DB11915.", + "ref-id: L2372; title: Toxicological Profile For Perchlorates; url: https://www.atsdr.cdc.gov/toxprofiles/tp162-c3.pdf; parent_key: DB09418." + ] + }, + { + "example_idx": 133, + "anchor_id": 14530232194285821845, + "positive_id": 1666810580147234926, + "join_paths": [ + [ + 6, + 25, + 0.287109375 + ], + [ + 6, + 0, + 0.283203125 + ], + [ + 6, + 2, + 0.28125 + ], + [ + 6, + 43, + 0.28125 + ], + [ + 6, + 49, + 0.28125 + ] + ], + "rows": [ + "Isothermal titration microcalorimetry has been used to measure changes in enthalpy and heat capacity for binding of lisinopril to the angiotensin I-converting enzyme (ACE; EC 3.4.15.1) and to its apoenzyme at pH 7.5 over a temperature range of 15-30 degrees C. Calorimetric measurements indicate that lisinopril binds to two sites in the monomer of both holo- and apo-ACE.", + "Binding of lisinopril to both systems is enthalpically unfavorable and, thus, is dominated by a large positive entropy change.", + "The enthalpy change of binding is strongly temperature-dependent for both holo- and apo-ACE, arising from a large heat capacity change of binding equal to -2.4 +/- 0.2 kJ/K/mol of monomeric holo-ACE) and to -1.9 +/- 0.2 kJ/K/mol of monomeric apo-ACE), respectively.", + "The negative values of deltaCp for both systems are consistent with burial of a large non-polar surface area upon binding.", + "Although the binding of lisinopril to holo- and apo-ACE is favored by entropy changes, this is more positive for the holoenzyme.", + "Thus, the interaction between Zn2+ and lisinopril results in a higher affinity of the holoenzyme for this drug due to a more favorable entropic contribution.", + "Angiotensin-Converting Enzyme Inhibitors\nAnimals\nApoenzymes\nCalorimetry\nCattle\nCoenzymes\nLisinopril\nPeptidyl-Dipeptidase A\nProtein Binding\nThermodynamics" + ], + "sentences": [ + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB01348.", + "id: BE0002716; name: Apocarotenoid-15,15'-oxygenase; organism: Synechocystis sp. (strain PCC 6803 / Kazusa); known_action: unknown; parent_key: DB02253.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB01197.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; parent_key: DB01349.", + "id: BE0001301; name: Monomeric sarcosine oxidase; organism: Bacillus sp. (strain B-0618); known_action: unknown; parent_key: DB03098.", + "id: BE0000982; name: Angiotensin-converting enzyme 2; organism: Humans; known_action: unknown; parent_key: DB05203.", + "id: BE0001281; name: Hut operon positive regulatory protein; organism: Bacillus subtilis (strain 168); known_action: unknown; parent_key: DB01938.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; parent_key: DB01342.", + "id: BE0000437; name: Cyclin-dependent kinase 15; organism: Humans; known_action: unknown; position: 243; parent_key: DB12010.", + "id: BE0000309; name: Arachidonate 15-lipoxygenase; organism: Humans; known_action: unknown; position: 1; parent_key: DB08492.", + "id: BE0000437; name: Cyclin-dependent kinase 15; organism: Humans; known_action: unknown; parent_key: DB00171.", + "id: BE0001301; name: Monomeric sarcosine oxidase; organism: Bacillus sp. (strain B-0618); known_action: unknown; parent_key: DB02083.", + "id: BE0001301; name: Monomeric sarcosine oxidase; organism: Bacillus sp. (strain B-0618); known_action: unknown; parent_key: DB03366.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; parent_key: DB00966.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00691.", + "id: BE0001898; name: Heat shock protein HSP 90-beta; organism: Humans; known_action: unknown; parent_key: DB05134.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00584.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: unknown; parent_key: DB02032.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00519.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; parent_key: DB00492.", + "id: BE0003382; name: Serine/threonine-protein kinase Chk1; organism: Humans; known_action: unknown; position: 1; parent_key: DB07243.", + "id: BE0000982; name: Angiotensin-converting enzyme 2; organism: Humans; known_action: unknown; position: 11; parent_key: DB00608.", + "id: BE0004524; name: Disks large homolog 4; organism: Humans; known_action: unknown; parent_key: DB01972.", + "id: BE0003426; name: Type-2 angiotensin II receptor; organism: Humans; known_action: unknown; position: 1; parent_key: DB01349.", + "id: BE0002372; name: Protein farnesyltransferase subunit beta; organism: Humans; known_action: unknown; position: 3; parent_key: DB07841.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB13166.", + "id: BE0003762; name: cAMP-dependent protein kinase inhibitor alpha; organism: Humans; known_action: unknown; position: 2; parent_key: DB07859.", + "id: BE0008650; name: Beta-lactamase CTX-M-15; organism: Escherichia coli; known_action: yes; position: 11; parent_key: DB09060.", + "id: BE0004574; name: ERO1-like protein beta; organism: Humans; known_action: unknown; parent_key: DB01902.", + "id: BE0000177; name: Sodium channel protein type 10 subunit alpha; organism: Humans; known_action: yes; parent_key: DB00296.", + "id: BE0001716; name: Protease synthase and sporulation negative regulatory protein PAI 1; organism: Bacillus subtilis (strain 168); known_action: unknown; parent_key: DB04447.", + "id: BE0001301; name: Monomeric sarcosine oxidase; organism: Bacillus sp. (strain B-0618); known_action: unknown; parent_key: DB01918.", + "id: BE0000982; name: Angiotensin-converting enzyme 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB15643.", + "id: BE0002396; name: Voltage-dependent calcium channel subunit alpha-2/delta-2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00996.", + "id: BE0001071; name: Tyrosine-protein phosphatase non-receptor type 11; organism: Humans; known_action: unknown; parent_key: DB02779.", + "id: BE0004618; name: Cell division control protein 42 homolog; organism: Humans; known_action: unknown; parent_key: DB02623.", + "id: BE0000552; name: 15-hydroxyprostaglandin dehydrogenase [NAD(+)]; organism: Humans; known_action: unknown; parent_key: DB00157.", + "id: BE0001301; name: Monomeric sarcosine oxidase; organism: Bacillus sp. (strain B-0618); known_action: unknown; parent_key: DB02543.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB13919.", + "id: BE0002809; name: Surface protein A; organism: Neisseria meningitidis; known_action: unknown; parent_key: DB03994.", + "id: BE0001018; name: Solute carrier family 15 member 1; organism: Humans; known_action: unknown; position: 14; parent_key: DB01053.", + "id: BE0001120; name: Heat shock protein HSP 90-alpha; organism: Humans; known_action: unknown; position: 1; parent_key: DB06964.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; parent_key: DB01347.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: yes; position: 1; parent_key: DB09477.", + "id: BE0001823; name: Holo-[acyl-carrier-protein] synthase; organism: Bacillus subtilis (strain 168); known_action: unknown; parent_key: DB04447.", + "id: BE0001148; name: Dipeptidase 1; organism: Humans; known_action: yes; parent_key: DB01597.", + "id: BE0000062; name: Type-1 angiotensin II receptor; organism: Humans; known_action: yes; position: 1; parent_key: DB11842.", + "id: BE0000437; name: Cyclin-dependent kinase 15; organism: Humans; known_action: unknown; parent_key: DB06486.", + "id: BE0009218; name: Merozoite surface protein 1; organism: Plasmodium falciparum (isolate CDC / Honduras); known_action: unknown; position: 136; parent_key: DB11638.", + "id: BE0000221; name: Angiotensin-converting enzyme; organism: Humans; known_action: unknown; position: 1; parent_key: DB00616." + ] + }, + { + "example_idx": 134, + "anchor_id": 10531378686924169277, + "positive_id": 14262164416540485391, + "join_paths": [ + [ + 0, + 34, + 0.25390625 + ], + [ + 0, + 9, + 0.2490234375 + ], + [ + 0, + 30, + 0.2412109375 + ], + [ + 0, + 41, + 0.2412109375 + ], + [ + 0, + 25, + 0.2265625 + ] + ], + "rows": [ + "Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to plasma membrane surfaces by a phosphatidylinositol glycan linkage.", + "We have determined the 2.8-angstroms resolution crystal structure of a truncated, soluble form of recombinant murine CAIV.", + "We have also determined the structure of its complex with a drug used for glaucoma therapy, the sulfonamide inhibitor brinzolamide (Azopt).", + "The overall structure of murine CAIV is generally similar to that of human CAIV; however, some local structural differences are found in the active site resulting from amino acid sequence differences in the \"130's segment\" and the residue-63 loop (these may affect the nearby catalytic proton shuttle, His-64).", + "Similar to human CAIV, the C-terminus of murine CAIV is surrounded by a substantial electropositive surface potential that may stabilize the interaction with the phospholipid membrane.", + "Binding interactions observed for brinzolamide rationalize the generally weaker affinity of inhibitors used in glaucoma therapy toward CAIV compared with CAII.", + "Amino Acid Sequence\nAnimals\nCarbonic Anhydrase Inhibitors\nCarbonic Anhydrases\nCrystallography, X-Ray\nGlycosylphosphatidylinositols\nHistidine\nHumans\nIsoenzymes\nMetalloproteins\nMice\nModels, Molecular\nMolecular Sequence Data\nProtein Structure, Tertiary\nStructure-Activity Relationship\nSulfonamides\nThiazines\nZinc" + ], + "sentences": [ + "id: BE0003625; name: Carbonic anhydrase 3; organism: Humans; known_action: unknown; position: 4; parent_key: DB00482.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB04089.", + "id: BE0001640; name: Phospholipase A2, membrane associated; organism: Humans; known_action: unknown; parent_key: DB04112.", + "id: BE0003709; name: 30S ribosomal protein S13; organism: Escherichia coli (strain K12); known_action: yes; position: 4; parent_key: DB00560.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB08645.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB08659.", + "id: BE0002408; name: Tyrosine-protein kinase JAK2; organism: Humans; known_action: unknown; parent_key: DB04716.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB02861.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: unknown; position: 7; parent_key: DB00273.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: unknown; position: 3; parent_key: DB01194.", + "id: BE0001640; name: Phospholipase A2, membrane associated; organism: Humans; known_action: unknown; position: 5; parent_key: DB03017.", + "id: BE0000795; name: Gamma-aminobutyric acid receptor subunit alpha-1; organism: Humans; known_action: yes; position: 1; parent_key: DB00273.", + "id: BE0001356; name: Tyrosine-protein kinase CSK; organism: Humans; known_action: unknown; position: 21; parent_key: DB01254.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB08165.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 1; parent_key: DB07476.", + "id: BE0003629; name: Carbonic anhydrase 7; organism: Humans; known_action: unknown; position: 1; parent_key: DB00774.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB03333.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: unknown; parent_key: DB04233.", + "id: BE0009972; name: Plasma membrane calcium-transporting ATPase; organism: Humans; known_action: yes; position: 20; parent_key: DB01159.", + "id: BE0008668; name: GABA(A) Receptor Benzodiazepine Binding Site; organism: Humans; known_action: yes; position: 2; parent_key: DB14715.", + "id: BE0000267; name: Carbonic anhydrase 1; organism: Humans; known_action: yes; parent_key: DB01325.", + "id: BE0003629; name: Carbonic anhydrase 7; organism: Humans; known_action: unknown; position: 12; parent_key: DB08846.", + "id: BE0004896; name: Membrane-associated progesterone receptor component 1; organism: Humans; known_action: unknown; position: 6; parent_key: DB00514.", + "id: BE0002437; name: Carbonic anhydrase 9; organism: Humans; known_action: unknown; position: 13; parent_key: DB08846.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: no; position: 9; parent_key: DB00695.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 16; parent_key: DB00909.", + "id: BE0003833; name: 60S ribosomal protein L3; organism: Humans; known_action: unknown; position: 13; parent_key: DB02494.", + "id: BE0003629; name: Carbonic anhydrase 7; organism: Humans; known_action: unknown; position: 22; parent_key: DB00909.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; position: 6; parent_key: DB08846.", + "id: BE0001640; name: Phospholipase A2, membrane associated; organism: Humans; known_action: unknown; parent_key: DB04287.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: unknown; position: 5; parent_key: DB00436.", + "id: BE0001570; name: Outer membrane protein F; organism: Escherichia coli (strain K12); known_action: unknown; position: 1; parent_key: DB07084.", + "id: BE0003346; name: Calpain-1 catalytic subunit; organism: Humans; known_action: unknown; parent_key: DB04653.", + "id: BE0001640; name: Phospholipase A2, membrane associated; organism: Humans; known_action: unknown; parent_key: DB03471.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: yes; position: 2; parent_key: DB01144.", + "id: BE0003625; name: Carbonic anhydrase 3; organism: Humans; known_action: unknown; position: 3; parent_key: DB00580.", + "id: BE0001122; name: Transient receptor potential cation channel subfamily A member 1; organism: Humans; known_action: yes; position: 3; parent_key: DB01744.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB03526.", + "id: BE0000576; name: Penicillin-binding protein 1A; organism: Clostridium perfringens (strain 13 / Type A); known_action: yes; parent_key: DB00417.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB02866.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB03904.", + "id: BE0000535; name: Carbonic anhydrase 4; organism: Humans; known_action: unknown; position: 8; parent_key: DB00774.", + "id: BE0001640; name: Phospholipase A2, membrane associated; organism: Humans; known_action: unknown; parent_key: DB02504.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB01748.", + "id: BE0002641; name: Peripheral plasma membrane protein CASK; organism: Humans; known_action: unknown; parent_key: DB01942.", + "id: BE0001640; name: Phospholipase A2, membrane associated; organism: Humans; known_action: unknown; position: 1; parent_key: DB02080.", + "id: BE0003089; name: ATP-dependent Clp protease ATP-binding subunit ClpX; organism: Helicobacter pylori (strain ATCC 700392 / 26695); known_action: unknown; position: 1; parent_key: DB09275.", + "id: BE0003936; name: Outer membrane protein G; organism: Escherichia coli (strain K12); known_action: unknown; position: 5; parent_key: DB04233.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: unknown; parent_key: DB03844.", + "id: BE0000322; name: Carbonic anhydrase 2; organism: Humans; known_action: yes; position: 1; parent_key: DB00869." + ] + }, + { + "example_idx": 135, + "anchor_id": 17968780180095871836, + "positive_id": 7899464319523055863, + "join_paths": [ + [ + 4, + 12, + 0.2099609375 + ], + [ + 4, + 33, + 0.2099609375 + ], + [ + 4, + 49, + 0.2099609375 + ], + [ + 4, + 26, + 0.208984375 + ], + [ + 4, + 30, + 0.208984375 + ] + ], + "rows": [ + "The in-vitro activities of five fluoroquinolones were tested against 70 ciprofloxacin-resistant and 46 ciprofloxacin-susceptible unrelated isolates of Staphylococcus aureus.", + "All 116 S. aureus isolates were studied for the presence of mutations in the grl and gyr loci.", + "The order of efficacy of the fluoroquinolones tested, from least to most active, was: ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039), in response to all characterized mutations in grlA, grlB, gyrA and gyrB.", + "Moxifloxacin was active against most S. aureus isolates tested (MIC90 = 1 mg/L for ciprofloxacin-resistant isolates) and was less influenced by known mutations.", + "Anti-Infective Agents\nCiprofloxacin\nDNA Gyrase\nDNA Topoisomerase IV\nDNA Topoisomerases, Type II\nDNA, Bacterial\nDrug Resistance, Microbial\nHumans\nMicrobial Sensitivity Tests\nMutation\nPolymerase Chain Reaction\nStaphylococcus aureus" + ], + "sentences": [ + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00276.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB14753.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01206.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01181.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB05109.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB05706.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04950.", + "id: BE0003836; name: Ig kappa chain C region; organism: Humans; known_action: unknown; position: 1; parent_key: DB08413.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00853.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01204.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB01702.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00515.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04992.", + "id: BE0009075; name: Coagulation factor XIII B chain; organism: Humans; known_action: yes; position: 5; parent_key: DB11300.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB03148.", + "id: BE0000721; name: Branched-chain-amino-acid aminotransferase, mitochondrial; organism: Humans; known_action: unknown; position: 10; parent_key: DB00142.", + "id: BE0009736; name: Polymerase acidic protein; organism: Influenza A virus (strain A/Puerto Rico/8/1934 H1N1); known_action: unknown; position: 4; parent_key: DB13997.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB04967.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00262.", + "id: BE0000623; name: Tyrosine-protein phosphatase non-receptor type 1; organism: Humans; known_action: unknown; parent_key: DB02615.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00406.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 5; parent_key: DB00544.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; position: 1; parent_key: DB15466.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB06328.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00987.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01008.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 2; parent_key: DB00709.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 4; parent_key: DB01041.", + "id: BE0003849; name: Photosynthetic reaction center cytochrome c subunit; organism: Rhodopseudomonas viridis; known_action: unknown; position: 1; parent_key: DB08215.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04996.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; position: 1; parent_key: DB02842.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB04961.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 2; parent_key: DB04572.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01177.", + "id: BE0000327; name: Melatonin receptor type 1B; organism: Humans; known_action: yes; parent_key: DB00980.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00432.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00249.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01611.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB01262.", + "id: BE0001367; name: Tubulin beta-4B chain; organism: Humans; known_action: unknown; parent_key: DB04910.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00442.", + "id: BE0000632; name: Kappa-type opioid receptor; organism: Humans; known_action: unknown; position: 8; parent_key: DB00289.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB06408.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; parent_key: DB00305.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 2; parent_key: DB13145.", + "id: BE0000716; name: DNA polymerase alpha subunit B; organism: Humans; known_action: unknown; position: 2; parent_key: DB00851.", + "id: BE0004796; name: DNA; organism: Humans; known_action: unknown; parent_key: DB02379.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB00694.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 3; parent_key: DB00928.", + "id: BE0004796; name: DNA; organism: Humans; known_action: yes; position: 1; parent_key: DB01099." + ] + }, + { + "example_idx": 136, + "anchor_id": 7976544020193917657, + "positive_id": 14344948030309648721, + "join_paths": [ + [ + 12, + 8, + 0.267578125 + ], + [ + 12, + 33, + 0.267578125 + ], + [ + 12, + 12, + 0.240234375 + ], + [ + 9, + 19, + 0.1884765625 + ], + [ + 10, + 28, + 0.1875 + ] + ], + "rows": [ + "1.", + "Alniditan, a novel migraine abortive agent, is a potent 5-HT1B/5-HT1D receptor agonist of nM affinity.", + "We compared the agonistic properties of alniditan, sumatriptan and dihydroergotamine on the cloned human 5-HT1B receptor expressed at 200 fmol mg(-1) protein (Bmax) in non-induced L929sA cells, at 740 fmol mg(-1) protein in HEK 293 and at 2300 fmol mg(-1) protein in mIFNbeta-induced L929sA cells, and on the human cloned 5-HT1D receptor expressed in C6 glioma cells (Bmax 780 fmol mg(-1) protein).", + "2.", + "Sodium butyrate treatment increased the expression level of human (h)5-HT1B receptors in HEK 293 cells and h5-HT1D receptors in C6 glioma cells approximately 3 fold, the binding affinities of [3H]-5-HT and [3H]-alniditan were unaffected.", + "3.", + "Agonistic properties were evaluated based on inhibition of cyclic AMP accumulation in the cells after stimulation of adenylyl cyclase by forskolin or isoproterenol.", + "Alniditan, sumatriptan and dihydroergotamine were full agonists at the hS-HT1B receptor (IC50 values were 1.7, 20 and 2 nM, respectively in HEK 293 cells) and hS-HT1D receptors (IC50 values of 1.3, 2.6 and 2.2 nM, respectively).", + "At the h5-HT1B receptor the agonist potency of the compounds slightly increased with higher receptor density.", + "The opposite was seen for antagonists (ocaperidone, risperidone and ritanserin).", + "4.", + "This comparative study demonstrated that alniditan was 10 times more potent than sumatriptan at the h5-HT1B receptor, and twice as potent at the h5-HT1D receptor.", + "Dihydroergotamine was more potent an agonist at the h5-HT1B receptor when expressed at high and low level in L929sA cells (but not in HEK 293 cells), and was less potent at the hS-HT1D receptor.", + "Adenylyl Cyclases\nAnimals\nBenzopyrans\nCell Line\nCell Membrane\nCloning, Molecular\nDihydroergotamine\nHumans\nLigands\nMice\nPropylamines\nPyrimidines\nRats\nReceptors, Serotonin\nSerotonin Receptor Agonists\nSignal Transduction\nSumatriptan\nVasoconstrictor Agents" + ], + "sentences": [ + "name: PHL-risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: Dromelate; ingredients: Dihydroergotamine; parent_key: DB00320.", + "name: Risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: Citrasate C2150; ingredients: Calcium chloride + Citric acid + Dextrose, unspecified form + Magnesium chloride + Potassium chloride + Sodium acetate + Sodium chloride; parent_key: DB00761.", + "name: Mixed Vespid hymenoptera venom Venomil Maintenance; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB10956.", + "name: Risperidone - 2; ingredients: Risperidone; parent_key: DB00734.", + "name: Premier Value Iodine Tincture Mild; ingredients: Ethanol + Iodine + Sodium iodide; parent_key: DB00898.", + "name: Mixed Vespid hymenoptera venom Venomil Maintenance; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11033.", + "name: Dihydroergotamine (dhe), 1mg/ml; ingredients: Dihydroergotamine; parent_key: DB00320.", + "name: PMS-risperidone ODT; ingredients: Risperidone; parent_key: DB00734.", + "name: Ipg-risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: Mixed Vespid Hymenoptera Venom Multidose; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11032.", + "name: Dihydroergotamine Mesylate Injection USP; ingredients: Dihydroergotamine; parent_key: DB00320.", + "name: SUEROLYTE Oral Electrolyte Solution Cherry Flavor; ingredients: D-glucose + Potassium citrate + Sodium chloride + Sodium chlorite + Zinc; parent_key: DB01914.", + "name: Ava-sumatriptan; ingredients: Sumatriptan; parent_key: DB00669.", + "name: UltraTag RBC; ingredients: Technetium Tc-99m red blood cells; parent_key: DB09493.", + "name: Ran-risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: Jamp-risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: Sumatriptan Succinate; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Riva-risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: Ratio-risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: PHL-sumatriptan; ingredients: Sumatriptan; parent_key: DB00669.", + "name: NESTABS DHA Prenatal Multi-vitamin/Mineral Supplement with DHA/EPA; ingredients: Calcium carbonate + Cholecalciferol + Choline + Cyanocobalamin + Doconexent + Ferrous bisglycinate + Folic acid + Formic acid + Icosapent + Nicotinamide + Potassium Iodide + Pyridoxine + Riboflavin + Sodium ascorbate + Thiamine + Tocopherylquinone + Vitamin E + Zinc oxide; parent_key: DB00159.", + "name: Sandoz Sumatriptan; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Imitrex Df - Tab 100mg; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Nu-sumatriptan; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Mixed Vespid hymenoptera venom Venomil Maintenance; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB11032.", + "name: Super Charged Energy; ingredients: Ascorbic acid + Beta carotene + Biotin + Calcium + Cholecalciferol + Cyanocobalamin + Folic acid + Magnesium + Nicotinamide + Pantothenic acid + Potassium + Potassium chloride + Pyridoxine + Riboflavin + Sodium phosphate, dibasic + Thiamine + Vitamin A + Vitamin E; parent_key: DB00152.", + "name: PR Natal 400 ec; ingredients: Ascorbic acid + Beta carotene + Calcium carbonate + Cholecalciferol + Cupric oxide + Cyanocobalamin + DL-alpha tocopheryl acetate + Ferrous bisglycinate + Folic acid + Iron protein succinylate + Magnesium oxide + Nicotinamide + Omega-3 fatty acids + Pyridoxine + Riboflavin + Thiamine + Zinc oxide; parent_key: DB02701.", + "name: Risperidone - 3; ingredients: Risperidone; parent_key: DB00734.", + "name: Teva-sumatriptan DF; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Dextrose 2.5% In Half Strength Lactated Ringer's Injection, USP; ingredients: Calcium chloride + Dextrose, unspecified form + Lactic acid + Potassium chloride + Sodium chloride; parent_key: DB00761.", + "name: Tqm Acid Concentrate A1280; ingredients: Acetic acid + Calcium chloride + Dextrose, unspecified form + Magnesium chloride + Potassium chloride + Sodium chloride; parent_key: DB00761.", + "name: Dihydroergotamine Mesylate; ingredients: Dihydroergotamine; parent_key: DB00320.", + "name: Q-risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: Risperidone Tablets; ingredients: Risperidone; parent_key: DB00734.", + "name: Apo-risperidone; ingredients: Risperidone; parent_key: DB00734.", + "name: Mint-risperidon; ingredients: Risperidone; parent_key: DB00734.", + "name: Migranal; ingredients: Dihydroergotamine; parent_key: DB00320.", + "name: Multivitamines Pour Enfants (chewable Tablets); ingredients: Cholecalciferol + Cyanocobalamin + Folic acid + Nicotinamide + Pyridoxine + Riboflavin + Sodium ascorbate + Thiamine + Vitamin A; parent_key: DB00152.", + "name: Imitrex Df - Tab 50mg; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Imitrex Df - Tab 25mg; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Imitrex Tab 100mg; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Tosymra; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Mixed Vespid hymenoptera venom Venomil Maintenance; ingredients: Dolichovespula arenaria venom protein + Dolichovespula maculata venom protein + Vespula germanica venom protein + Vespula maculifrons venom protein + Vespula pensylvanica venom protein + Vespula squamosa venom protein + Vespula vulgaris venom protein; parent_key: DB10957.", + "name: Cervarix; ingredients: Human papillomavirus type 16 L1 capsid protein residues 2-471 antigen + Human papillomavirus type 18 l1 capsid protein residues 2-472 antigen; parent_key: DB10994.", + "name: Apo-sumatriptan; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Risperidone - 1; ingredients: Risperidone; parent_key: DB00734.", + "name: Taro-sumatriptan; ingredients: Sumatriptan; parent_key: DB00669.", + "name: Risperidone - 0.5; ingredients: Risperidone; parent_key: DB00734." + ] + }, + { + "example_idx": 137, + "anchor_id": 16902269165821972143, + "positive_id": 647868568756689000, + "join_paths": [ + [ + 3, + 3, + 0.333984375 + ], + [ + 3, + 26, + 0.326171875 + ], + [ + 3, + 44, + 0.3203125 + ], + [ + 4, + 3, + 0.3125 + ], + [ + 3, + 24, + 0.310546875 + ] + ], + "rows": [ + "In vitro radioligand binding studies were carried out in rat brain membranes to assess the affinity of various reuptake inhibitors for the serotonin (5-hydroxytryptamine, 5-HT) and the norepinephrine transporters using the selective ligands [3H]cyanoimipramine and [3H]nisoxetine, respectively.", + "The selective 5-HT reuptake inhibitors paroxetine, indalpine and fluvoxamine displayed a high affinity for the 5-HT transporter, whereas the norepinephrine reuptake inhibitor desipramine had a high affinity for the norepinephrine transporter.", + "Duloxetine, a dual 5-HT and norepinephrine reuptake inhibitor, displayed a high affinity for both the 5-HT and the norepinephrine transporters.", + "Interestingly, venlafaxine, a dual 5-HT and norepinephrine reuptake inhibitor, displayed only a moderate affinity for the 5-HT transporter (Ki = 74 nM) and a very low affinity for the norepinephrine transporter (Ki = 1.26 microM).", + "The relatively low affinities of venlafaxine contrast with its potent in vivo 5-HT and norepinephrine reuptake blocking properties.", + "These results raise the possibility that the in vivo effects on the 5-HT and norepinephrine reuptake observed with venlafaxine may not be mediated solely by its binding to the [3H]cyanoimipramine and [3H]nisoxetine binding sites.", + "Animals\nAntidepressive Agents, Second-Generation\nBinding, Competitive\nBrain\nCarrier Proteins\nCyclohexanols\nFluoxetine\nImipramine\nMale\nMembrane Glycoproteins\nMembrane Transport Proteins\nNerve Tissue Proteins\nNeurotransmitter Uptake Inhibitors\nNorepinephrine\nNorepinephrine Plasma Membrane Transport Proteins\nRadioligand Assay\nRats\nRats, Sprague-Dawley\nSerotonin\nSerotonin Antagonists\nSerotonin Plasma Membrane Transport Proteins\nSerotonin Uptake Inhibitors\nSymporters\nVenlafaxine Hydrochloride" + ], + "sentences": [ + "name: Xeristar; ingredients: Duloxetine; parent_key: DB00476.", + "name: Riva-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Effexor Tablets, 50mg; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Venlafaxine; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Cymbalta; ingredients: Duloxetine; parent_key: DB00476.", + "name: Proderm; ingredients: Balsam of Peru + Castor oil; parent_key: DB11113.", + "name: Levophed Liq IV 1.0mg/ml; ingredients: Norepinephrine; parent_key: DB00368.", + "name: PMS-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Norepinephrine Bitartrate; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Apo-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: PHL-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Auro-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Teva-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Effexor Tablets, 75mg; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Taro-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Medical Provider Single Use EZ Flu Shot Kit; ingredients: Influenza A virus A/Christchurch/16/2010 NIB-74 (H1N1) antigen (propiolactone inactivated) + Influenza A virus A/Victoria/361/2011 IVR-165 (H3N2) antigen (propiolactone inactivated) + Influenza B virus B/Hubei-Wujiagang/158/2009 BX-39 antigen (propiolactone inactivated); parent_key: DB10781.", + "name: Norepinephrine Bitartrate Injection USP; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Symbyax; ingredients: Fluoxetine + Olanzapine; parent_key: DB00334.", + "name: Effexor XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: M-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Duloxetine Lilly; ingredients: Duloxetine; parent_key: DB00476.", + "name: Venlafaxine Hydrochloride Extended-release Capsules; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Duloxetine Zentiva; ingredients: Duloxetine; parent_key: DB00476.", + "name: Levophed; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Proderm; ingredients: Balsam of Peru + Castor oil; parent_key: DB11482.", + "name: Venlafaxine Hydrochloride; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Effexor XR Extended-Release; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Prozac Capsules 20mg; ingredients: Fluoxetine; parent_key: DB00472.", + "name: Ntp-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Duloxetine Mylan; ingredients: Duloxetine; parent_key: DB00476.", + "name: Ratio-desipramine Tab 75mg; ingredients: Desipramine; parent_key: DB01151.", + "name: PMS Desipramine Hydro Tab 75mg; ingredients: Desipramine; parent_key: DB01151.", + "name: Sandoz Venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Gd-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Norepinephrine Bitartrate Inj 1mg/ml USP; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Dom-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Levophed(r) Norepinephrine Bitartrate; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Norepinephrine Bitartrate Injection, USP; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Act Venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Norepinephrine; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Gaboxetine; ingredients: Choline + Fluoxetine; parent_key: DB00122.", + "name: Imipramine Hydrochloride; ingredients: Imipramine; parent_key: DB00458.", + "name: Chi-Myst Topical; ingredients: Bupivacaine + Chitosan low molecular weight (20-200 mpa.s) + Ketorolac; parent_key: DB14155.", + "name: Venlafaxine hydrochloride; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Effexor; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Effexor Tablets, 37.5mg; ingredients: Venlafaxine; parent_key: DB00285.", + "name: Norepinephrine bitartrate; ingredients: Norepinephrine; parent_key: DB00368.", + "name: Ariclaim; ingredients: Duloxetine; parent_key: DB00476.", + "name: Mylan-venlafaxine XR; ingredients: Venlafaxine; parent_key: DB00285." + ] + }, + { + "example_idx": 139, + "anchor_id": 16605100369037609979, + "positive_id": 8160138113901636932, + "join_paths": [ + [ + 9, + 44, + 0.330078125 + ], + [ + 2, + 26, + 0.326171875 + ], + [ + 9, + 19, + 0.32421875 + ], + [ + 9, + 26, + 0.31640625 + ], + [ + 9, + 42, + 0.314453125 + ] + ], + "rows": [ + "Oatp1, the organic anion transport polypeptide, is an integral membrane protein cloned from rat liver that mediates the uptake of various organic anions such as bromosulfophthalein (BSP) and taurocholate (TCA).", + "Recent studies by others revealed that the thrombin inhibitor, CRC 220, a modified dipeptide, was transported by oatp1.", + "The present study was designed to examine whether another modified peptide, enalapril, an angiotensin-converting enzyme inhibitor, was also a substrate.", + "Transport was studied with enalapril (1 to 800 micromol/L, with [3H]enalapril) in a HeLa cell line stably transfected with oatp1-cDNA under the regulation of a Zn2+-inducible promoter.", + "Noninduced transfected cells (without zinc) that did not express oatp1 failed to take up enalapril.", + "In contrast, cells expressing oatp1 transported enalapril, estrone sulfate (E1S), taurolithocholic acid sulfate (TLCAS), and the glutathione conjugate of BSP (BSPGSH).", + "Uptake of enalapril by oatp1 at 37 degreesC was substantially higher than that at 4 degreesC.", + "The rate at 37 degreesC (uptake rates for induced - noninduced, transfected cells) was linear over 5 minutes and was concentration-dependent, characterized by a Km of 214 +/- 67 micromol/L and a Vmax of 0.51 +/- 0.15 nmol/min/mg protein.", + "Enalapril uptake was inhibited competitively by BSP (at 1, 5, 10, and 50 micromol/L) and TCA (at 5, 25, and 100 micromol/L) with inhibition constants (Ki) of 2 and 32 micromol/L, respectively.", + "The metabolite enalaprilat was, however, not transported by oatp1.", + "That oatp1 is not a general transporter of anionic compounds was further shown by the lack of transport of harmol sulfate, benzoate, and hippurate.", + "These observations attest to the role of oatp1 as a specific transporter for at least two classes of pharmacologically important peptides.", + "Angiotensin-Converting Enzyme Inhibitors\nAnimals\nAnion Transport Proteins\nAnions\nBiological Transport\nCarbon Radioisotopes\nCarrier Proteins\nEnalapril\nEstrone\nGene Expression\nGlutathione\nHeLa Cells\nHumans\nPromoter Regions, Genetic\nRats\nSulfobromophthalein\nTaurocholic Acid\nTaurolithocholic Acid\nTransfection\nTritium\nZinc" + ], + "sentences": [ + "drugbank-id: DB00584; name: Enalapril; description: The excretion of Cephalexin can be decreased when combined with Enalapril.; parent_key: DB00567.", + "drugbank-id: DB11268; name: Protocatechualdehyde; description: The risk or severity of bleeding can be increased when Protocatechualdehyde is combined with Alteplase.; parent_key: DB00009.", + "drugbank-id: DB00394; name: Beclomethasone dipropionate; description: The risk or severity of hyperglycemia can be increased when Beclomethasone dipropionate is combined with Gastric inhibitory polypeptide.; parent_key: DB15217.", + "drugbank-id: DB09477; name: Enalaprilat; description: Topiroxostat may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB01685.", + "drugbank-id: DB09477; name: Enalaprilat; description: Ephedrine may decrease the antihypertensive activities of Enalaprilat.; parent_key: DB01364.", + "drugbank-id: DB10389; name: Lolium perenne pollen; description: The risk of a hypersensitivity reaction to Lolium perenne pollen is increased when it is combined with Landiolol.; parent_key: DB12212.", + "drugbank-id: DB04574; name: Estrone sulfate; description: The serum concentration of Oxaprotiline can be increased when it is combined with Estrone sulfate.; parent_key: DB09307.", + "drugbank-id: DB09477; name: Enalaprilat; description: Cefazolin may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB01327.", + "drugbank-id: DB09477; name: Enalaprilat; description: The risk or severity of hyperkalemia can be increased when Bufuralol is combined with Enalaprilat.; parent_key: DB06726.", + "drugbank-id: DB04574; name: Estrone sulfate; description: Azelaic acid may decrease the excretion rate of Estrone sulfate which could result in a higher serum level.; parent_key: DB00548.", + "drugbank-id: DB09477; name: Enalaprilat; description: Trimethoprim may increase the hyperkalemic activities of Enalaprilat.; parent_key: DB00440.", + "drugbank-id: DB09477; name: Enalaprilat; description: Clopamide may increase the excretion rate of Enalaprilat which could result in a lower serum level and potentially a reduction in efficacy.; parent_key: DB13792.", + "drugbank-id: DB09477; name: Enalaprilat; description: Dienogest may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB09123.", + "drugbank-id: DB00584; name: Enalapril; description: Desipramine may decrease the antihypertensive activities of Enalapril.; parent_key: DB01151.", + "drugbank-id: DB04574; name: Estrone sulfate; description: The serum concentration of Estrone sulfate can be increased when it is combined with Betamethasone.; parent_key: DB00443.", + "drugbank-id: DB09477; name: Enalaprilat; description: Vilanterol may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB09082.", + "drugbank-id: DB09477; name: Enalaprilat; description: Cefatrizine may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB13266.", + "drugbank-id: DB09477; name: Enalaprilat; description: Acetaminophen may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB00316.", + "drugbank-id: DB09477; name: Enalaprilat; description: Chlorzoxazone may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB00356.", + "drugbank-id: DB09477; name: Enalaprilat; description: The risk or severity of angioedema can be increased when Omapatrilat is combined with Enalaprilat.; parent_key: DB00886.", + "drugbank-id: DB12455; name: Omadacycline; description: Zinc chloride can cause a decrease in the absorption of Omadacycline resulting in a reduced serum concentration and potentially a decrease in efficacy.; parent_key: DB14533.", + "drugbank-id: DB09477; name: Enalaprilat; description: Imipramine may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB00458.", + "drugbank-id: DB09477; name: Enalaprilat; description: The risk or severity of angioedema can be increased when Anistreplase is combined with Enalaprilat.; parent_key: DB00029.", + "drugbank-id: DB04574; name: Estrone sulfate; description: The metabolism of Estrone sulfate can be increased when combined with Calcitriol.; parent_key: DB00136.", + "drugbank-id: DB13225; name: Dibenzepin; description: The therapeutic efficacy of Dibenzepin can be increased when used in combination with Magnesium sulfate.; parent_key: DB00653.", + "drugbank-id: DB09477; name: Enalaprilat; description: The risk or severity of angioedema can be increased when Ramipril is combined with Enalaprilat.; parent_key: DB00178.", + "drugbank-id: DB00584; name: Enalapril; description: The excretion of Enalapril can be decreased when combined with Novobiocin.; parent_key: DB01051.", + "drugbank-id: DB04574; name: Estrone sulfate; description: The serum concentration of Formocortal can be increased when it is combined with Estrone sulfate.; parent_key: DB13664.", + "drugbank-id: DB04574; name: Estrone sulfate; description: The metabolism of Estrone sulfate can be increased when combined with Sulthiame.; parent_key: DB08329.", + "drugbank-id: DB09477; name: Enalaprilat; description: Cyclosporine may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB00091.", + "drugbank-id: DB09477; name: Enalaprilat; description: Dibekacin may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB13270.", + "drugbank-id: DB09477; name: Enalaprilat; description: Liothyronine may decrease the excretion rate of Enalaprilat which could result in a higher serum level.; parent_key: DB00279.", + "drugbank-id: DB09477; name: Enalaprilat; description: Flupentixol may decrease the antihypertensive activities of Enalaprilat.; parent_key: DB00875.", + "drugbank-id: DB06366; name: Pertuzumab; description: The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Pertuzumab.; parent_key: DB00012.", + "drugbank-id: DB05996; name: Glembatumumab vedotin; description: Estradiol benzoate may increase the thrombogenic activities of Glembatumumab vedotin.; parent_key: DB13953.", + "drugbank-id: DB00584; name: Enalapril; description: The risk or severity of hyperkalemia can be increased when Enalapril is combined with Carvedilol.; parent_key: DB01136.", + "drugbank-id: DB00584; name: Enalapril; description: The risk or severity of hyperkalemia can be increased when Enalapril is combined with Nebivolol.; parent_key: DB04861.", + "drugbank-id: DB00584; name: Enalapril; description: The risk or severity of angioedema can be increased when Tenecteplase is combined with Enalapril.; parent_key: DB00031.", + "drugbank-id: DB00584; name: Enalapril; description: The excretion of Enalapril can be decreased when combined with Clofarabine.; parent_key: DB00631.", + "drugbank-id: DB05915; name: MYO-029; description: Estradiol benzoate may increase the thrombogenic activities of MYO-029.; parent_key: DB13953.", + 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reduction in efficacy.; parent_key: DB00007.", + "drugbank-id: DB00584; name: Enalapril; description: Sildenafil may increase the antihypertensive activities of Enalapril.; parent_key: DB00203.", + "drugbank-id: DB14449; name: Influenza A virus A/Perth/16/2009 (H3N2) live (attenuated) antigen; description: The therapeutic efficacy of Influenza A virus A/Perth/16/2009 (H3N2) live (attenuated) antigen can be decreased when used in combination with Interferon alfa-n1.; parent_key: DB00011.", + "drugbank-id: DB09477; name: Enalaprilat; description: Droperidol may decrease the antihypertensive activities of Enalaprilat.; parent_key: DB00450.", + "drugbank-id: DB09477; name: Enalaprilat; description: The risk or severity of angioedema can be increased when Enalaprilat is combined with Quinaprilat.; parent_key: DB14217." + ] + } +] \ No newline at end of file diff --git a/Exp-2/models/LOKI/sentence-transformers/embeddinggemma-300m-medical/best_model_epoch_9/model.pt 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b/Exp-2/models/LOKI/visualizations/diagnostics_example_1/step6_final_pair_scores.png @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:4f3f6fa692caab74010157293e48baf2e4f0ceafae10d1516d9a85fd01556340 +size 879450 diff --git a/Exp-2/models/LOKI/visualizations/diagnostics_example_1/validation_report_example_1.txt b/Exp-2/models/LOKI/visualizations/diagnostics_example_1/validation_report_example_1.txt new file mode 100644 index 0000000000000000000000000000000000000000..06a06e5ce13184f1f8b46545372f6b455dafa8cf --- /dev/null +++ b/Exp-2/models/LOKI/visualizations/diagnostics_example_1/validation_report_example_1.txt @@ -0,0 +1,158 @@ +=== DIAGNOSTIC VALIDATION REPORT === +Example: 1 +Model Type: Bidirectional +Rows: 10, Sentences: 50 +Generated: 2026-09-04 12:32:35.902049 + +=== ATTENTION NORMALIZATION CHECKS === +Forward attention row sums (should be ~1.0): + Row 1: 0.999023 + Row 2: 1.000000 + Row 3: 1.000000 + Row 4: 0.999023 + Row 5: 1.000000 + Row 6: 1.000977 + Row 7: 0.999023 + Row 8: 0.999023 + Row 9: 1.000000 + Row 10: 1.000000 + +Reverse attention column sums (should be ~1.0): + Sentence 1: 5.178711 + Sentence 2: 7.611328 + Sentence 3: 2.596680 + Sentence 4: 8.611328 + Sentence 5: 8.000977 + Sentence 6: 1.599609 + Sentence 7: 2.393555 + Sentence 8: 8.627930 + Sentence 9: 2.987305 + Sentence 10: 2.405273 + +=== SCORE RANGE VALIDATION === +Raw similarities: [-0.021973, 0.566406] +Forward attention: [0.000000, 0.209961] +Reverse attention: [0.000000, 0.202148] +Final pair scores: [-0.068848, 0.161133] + +=== TOP 3 PAIRS ANALYSIS === + +Top 3 by Raw Similarities: + 1. Row 10 - Sentence 8 (Score: 0.566406) + Row: ATP Binding Cassette Transporter, Subfamily B, Member 1 +Animals +Anion Transport Proteins +Biological ... + Sentence: id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unk... + + 2. Row 5 - Sentence 10 (Score: 0.554688) + Row: P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a... + Sentence: id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: no; position: 6; parent_key: ... + + 3. Row 5 - Sentence 24 (Score: 0.546875) + Row: P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a... + Sentence: id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 5; parent_... + +Top 3 by Final Model Scores: + 1. Row 10 - Sentence 8 (Score: 0.161133) + Row: ATP Binding Cassette Transporter, Subfamily B, Member 1 +Animals +Anion Transport Proteins +Biological ... + Sentence: id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unk... + + 2. Row 4 - Sentence 9 (Score: 0.147461) + Row: On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (N... + Sentence: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; positi... + + 3. Row 4 - Sentence 37 (Score: 0.146484) + Row: On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (N... + Sentence: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; positi... + +=== MATRIX STATISTICS === +Raw similarities - Mean: 0.212502, Std: 0.129748 +Final scores - Mean: 0.023606, Std: 0.049349 +Learning effect (Final - Raw) - Mean: -0.188896 +Correlation between raw and final scores: 0.885004 + +=== ACTUAL CONTENT === +Table Rows: + Row 1: Fexofenadine, a nonsedating antihistamine, does not undergo significant metabolic biotransformation. + Row 2: Accordingly, it was hypothesized that uptake and efflux transporters could be importantly involved in the drug's disposition. + Row 3: Utilizing a recombinant vaccinia expression system, members of the organic anion transporting polypeptide family, such as the human organic anion transporting polypeptide (OATP) and rat organic anion transporting polypeptides 1 and 2 (Oatp1 and Oatp2), were found to mediate [(14)C]fexofenadine cellular uptake. + Row 4: On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (NTCP) and the rat organic cation transporter rOCT1 did not exhibit such activity. + Row 5: P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a polarized epithelial cell line lacking P-gp, and the derivative cell line (L-MDR1), which overexpresses P-gp. + Row 6: In addition, oral and i.v. + Row 7: administration of [(14)C]fexofenadine to mice lacking mdr1a-encoded P-gp resulted in 5- and 9-fold increases in the drug's plasma and brain levels, respectively, compared with wild-type mice. + Row 8: Also, a number of drug inhibitors of P-gp were found to be effective inhibitors of OATP. + Row 9: Because OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine's disposition and suggests potentially similar roles in the disposition of other xenobiotics. + Row 10: ATP Binding Cassette Transporter, Subfamily B, Member 1 +Animals +Anion Transport Proteins +Biological Transport, Active +Caco-2 Cells +Carrier Proteins +Genes, MDR +HeLa Cells +Histamine H1 Antagonists +Humans +LLC-PK1 Cells +Mice +Rats +Swine +Terfenadine +Tissue Distribution +Transfection +Vaccinia virus + +Sentences: + Sentence 1: id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB00958. + Sentence 2: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 23; parent_key: DB04348. + Sentence 3: id: BE0004769; name: Y+L amino acid transporter 1; organism: Humans; known_action: unknown; position: 6; parent_key: DB00130. + Sentence 4: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 9; parent_key: DB09100. + Sentence 5: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB00091. + Sentence 6: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 12; parent_key: DB00795. + Sentence 7: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 11; parent_key: DB14761. + Sentence 8: id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 16; parent_key: DB13943. + Sentence 9: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13944. + Sentence 10: id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: no; position: 6; parent_key: DB01117. + Sentence 11: id: BE0003666; name: Copper-transporting ATPase 1; organism: Humans; known_action: no; position: 10; parent_key: DB09130. + Sentence 12: id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: no; position: 11; parent_key: DB09130. + Sentence 13: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB01586. + Sentence 14: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 3; parent_key: DB01098. + Sentence 15: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 3; parent_key: DB02123. + Sentence 16: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 1; parent_key: DB13153. + Sentence 17: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 1; parent_key: DB00887. + Sentence 18: id: BE0004769; name: Y+L amino acid transporter 1; organism: Humans; known_action: unknown; position: 11; parent_key: DB08838. + Sentence 19: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB01586. + Sentence 20: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 4; parent_key: DB02123. + Sentence 21: id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00945. + Sentence 22: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 20; parent_key: DB00328. + Sentence 23: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 12; parent_key: DB01098. + Sentence 24: id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB01244. + Sentence 25: id: BE0003666; name: Copper-transporting ATPase 1; organism: Humans; known_action: unknown; position: 15; parent_key: DB00526. + Sentence 26: id: BE0000106; name: Solute carrier family 22 member 5; organism: Humans; known_action: unknown; position: 1; parent_key: DB01208. + Sentence 27: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 5; parent_key: DB08912. + Sentence 28: id: BE0001134; name: Solute carrier family 15 member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB01140. + Sentence 29: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 11; parent_key: DB06290. + Sentence 30: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13946. + Sentence 31: id: BE0003645; name: Solute carrier family 22 member 8; organism: Humans; known_action: unknown; position: 11; parent_key: DB02659. + Sentence 32: id: BE0009872; name: Y+L amino acid transporter 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB00130. + Sentence 33: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 8; parent_key: DB01583. + Sentence 34: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00451. + Sentence 35: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 9; parent_key: DB08860. + Sentence 36: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 12; parent_key: DB01032. + Sentence 37: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13943. + Sentence 38: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB00286. + Sentence 39: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 4; parent_key: DB00787. + Sentence 40: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00646. + Sentence 41: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB04348. + Sentence 42: id: BE0009680; name: B-cell antigen receptor complex-associated protein beta chain; organism: Humans; known_action: unknown; position: 2; parent_key: DB12240. + Sentence 43: id: BE0000106; name: Solute carrier family 22 member 5; organism: Humans; known_action: unknown; position: 3; parent_key: DB14754. + Sentence 44: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 7; parent_key: DB09102. + Sentence 45: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB00091. + Sentence 46: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB00279. + Sentence 47: id: BE0003642; name: Solute carrier organic anion transporter family member 1A2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00635. + Sentence 48: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB00396. + Sentence 49: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 2; parent_key: DB00977. + Sentence 50: id: BE0000732; name: Sodium/potassium-transporting ATPase subunit alpha-1; organism: Humans; known_action: unknown; position: 2; parent_key: DB14500. diff --git a/Exp-2/models/LOKI/visualizations/example_1_similarity_analysis.txt b/Exp-2/models/LOKI/visualizations/example_1_similarity_analysis.txt new file mode 100644 index 0000000000000000000000000000000000000000..fc22a7e62643dde58048e607c8dd54d67da0c064 --- /dev/null +++ b/Exp-2/models/LOKI/visualizations/example_1_similarity_analysis.txt @@ -0,0 +1,587 @@ +=== Comprehensive Similarity Analysis - Example 1 === +Model Type: Bidirectional +Aggregation Method: top_k_pairs +Pair Score Method: cosine + +TABLE ROWS: +Row 1: Fexofenadine, a nonsedating antihistamine, does not undergo significant metabolic biotransformation. +Row 2: Accordingly, it was hypothesized that uptake and efflux transporters could be importantly involved in the drug's disposition. +Row 3: Utilizing a recombinant vaccinia expression system, members of the organic anion transporting polypeptide family, such as the human organic anion transporting polypeptide (OATP) and rat organic anion transporting polypeptides 1 and 2 (Oatp1 and Oatp2), were found to mediate [(14)C]fexofenadine cellular uptake. +Row 4: On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (NTCP) and the rat organic cation transporter rOCT1 did not exhibit such activity. +Row 5: P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a polarized epithelial cell line lacking P-gp, and the derivative cell line (L-MDR1), which overexpresses P-gp. +Row 6: In addition, oral and i.v. +Row 7: administration of [(14)C]fexofenadine to mice lacking mdr1a-encoded P-gp resulted in 5- and 9-fold increases in the drug's plasma and brain levels, respectively, compared with wild-type mice. +Row 8: Also, a number of drug inhibitors of P-gp were found to be effective inhibitors of OATP. +Row 9: Because OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine's disposition and suggests potentially similar roles in the disposition of other xenobiotics. +Row 10: ATP Binding Cassette Transporter, Subfamily B, Member 1 +Animals +Anion Transport Proteins +Biological Transport, Active +Caco-2 Cells +Carrier Proteins +Genes, MDR +HeLa Cells +Histamine H1 Antagonists +Humans +LLC-PK1 Cells +Mice +Rats +Swine +Terfenadine +Tissue Distribution +Transfection +Vaccinia virus + +CONTEXT SENTENCES: +Sent 1: id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: unknown; position: 4; parent_key: DB00958. +Sent 2: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 23; parent_key: DB04348. +Sent 3: id: BE0004769; name: Y+L amino acid transporter 1; organism: Humans; known_action: unknown; position: 6; parent_key: DB00130. +Sent 4: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 9; parent_key: DB09100. +Sent 5: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB00091. +Sent 6: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 12; parent_key: DB00795. +Sent 7: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 11; parent_key: DB14761. +Sent 8: id: BE0001067; name: ATP-binding cassette sub-family G member 2; organism: Humans; known_action: unknown; position: 16; parent_key: DB13943. +Sent 9: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13944. +Sent 10: id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: no; position: 6; parent_key: DB01117. +Sent 11: id: BE0003666; name: Copper-transporting ATPase 1; organism: Humans; known_action: no; position: 10; parent_key: DB09130. +Sent 12: id: BE0003664; name: Copper-transporting ATPase 2; organism: Humans; known_action: no; position: 11; parent_key: DB09130. +Sent 13: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB01586. +Sent 14: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 3; parent_key: DB01098. +Sent 15: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 3; parent_key: DB02123. +Sent 16: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 1; parent_key: DB13153. +Sent 17: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 1; parent_key: DB00887. +Sent 18: id: BE0004769; name: Y+L amino acid transporter 1; organism: Humans; known_action: unknown; position: 11; parent_key: DB08838. +Sent 19: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB01586. +Sent 20: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 4; parent_key: DB02123. +Sent 21: id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00945. +Sent 22: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 20; parent_key: DB00328. +Sent 23: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 12; parent_key: DB01098. +Sent 24: id: BE0001032; name: P-glycoprotein 1; organism: Humans; known_action: unknown; position: 5; parent_key: DB01244. +Sent 25: id: BE0003666; name: Copper-transporting ATPase 1; organism: Humans; known_action: unknown; position: 15; parent_key: DB00526. +Sent 26: id: BE0000106; name: Solute carrier family 22 member 5; organism: Humans; known_action: unknown; position: 1; parent_key: DB01208. +Sent 27: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 5; parent_key: DB08912. +Sent 28: id: BE0001134; name: Solute carrier family 15 member 2; organism: Humans; known_action: unknown; position: 2; parent_key: DB01140. +Sent 29: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 11; parent_key: DB06290. +Sent 30: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13946. +Sent 31: id: BE0003645; name: Solute carrier family 22 member 8; organism: Humans; known_action: unknown; position: 11; parent_key: DB02659. +Sent 32: id: BE0009872; name: Y+L amino acid transporter 2; organism: Humans; known_action: unknown; position: 7; parent_key: DB00130. +Sent 33: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 8; parent_key: DB01583. +Sent 34: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 5; parent_key: DB00451. +Sent 35: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 9; parent_key: DB08860. +Sent 36: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 12; parent_key: DB01032. +Sent 37: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 13; parent_key: DB13943. +Sent 38: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB00286. +Sent 39: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 4; parent_key: DB00787. +Sent 40: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 2; parent_key: DB00646. +Sent 41: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB04348. +Sent 42: id: BE0009680; name: B-cell antigen receptor complex-associated protein beta chain; organism: Humans; known_action: unknown; position: 2; parent_key: DB12240. +Sent 43: id: BE0000106; name: Solute carrier family 22 member 5; organism: Humans; known_action: unknown; position: 3; parent_key: DB14754. +Sent 44: id: BE0001004; name: Solute carrier organic anion transporter family member 1B1; organism: Humans; known_action: unknown; position: 7; parent_key: DB09102. +Sent 45: id: BE0003643; name: Ileal sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 6; parent_key: DB00091. +Sent 46: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 5; parent_key: DB00279. +Sent 47: id: BE0003642; name: Solute carrier organic anion transporter family member 1A2; organism: Humans; known_action: unknown; position: 2; parent_key: DB00635. +Sent 48: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 7; parent_key: DB00396. +Sent 49: id: BE0003644; name: Sodium/bile acid cotransporter; organism: Humans; known_action: unknown; position: 2; parent_key: DB00977. +Sent 50: id: BE0000732; name: Sodium/potassium-transporting ATPase subunit alpha-1; organism: Humans; known_action: unknown; position: 2; parent_key: DB14500. + +=== SIMILARITY MATRICES === + +RAW EMBEDDINGS (Sentence Encoder): +[[ 4.58984375e-02 8.44726562e-02 7.66601562e-02 8.69140625e-02 + 8.15429688e-02 7.47070312e-02 7.37304688e-02 -1.31607056e-04 + 7.71484375e-02 1.46484375e-01 3.75976562e-02 4.88281250e-02 + 7.95898438e-02 7.95898438e-02 8.30078125e-02 8.25195312e-02 + 8.83789062e-02 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