{"id":"W2963558305","doi":"10.1016/j.neuropharm.2019.107718","title":"Biased agonism of clinically approved μ-opioid receptor agonists and TRV130 is not controlled by binding and signaling kinetics","year":2019,"lang":"en","type":"article","venue":"Neuropharmacology","topic":"Receptor Mechanisms and Signaling","field":"Biochemistry, Genetics and Molecular Biology","cited_by":80,"is_retracted":false,"has_abstract":true,"ca_institutions":"Institute for Research in Immunology and Cancer; Université de Montréal","funders":"H2020 Marie Skłodowska-Curie Actions; Danmarks Frie Forskningsfond; Canadian Institutes of Health Research; Knud Højgaards Fond; Oticon Fonden; H. Lundbeck A/S; Augustinus Fonden; Lundbeckfonden; Carlsbergfondet; European Commission; Toyota Foundation","keywords":"Pharmacology; Agonist; G protein-coupled receptor; Receptor–ligand kinetics; Buprenorphine; Opioid receptor; Internalization; Receptor; Opioid; Functional selectivity; Chemistry; Medicine; Internal medicine","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0003501427,0.0002450758,0.0005448809,0.00006317216,0.00006555779,0.00002935487,0.0001681509,0.0002604993,0.0003512283],"category_scores_gemma":[0.0001399473,0.0002309484,0.0001148015,0.00006635628,0.0001349518,0.000005308063,0.0001451003,0.0001980733,0.000008455901],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000006549074,"about_ca_system_score_gemma":0.00004428181,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000005156703,"about_ca_topic_score_gemma":2.361576e-7,"domain_scores_codex":[0.9981211,0.000215266,0.0006245419,0.0005848996,0.0001372572,0.0003169312],"domain_scores_gemma":[0.9990091,0.0002113036,0.0003419483,0.0001922553,0.00009764313,0.000147786],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.001407501,0.00008439653,0.0004549746,0.00005068679,0.00009784076,0.000002660901,0.00005582711,0.00004501458,0.995908,0.00001212135,0.0007741968,0.001106778],"study_design_scores_gemma":[0.007618773,0.001724316,0.00002671029,0.00001201213,0.00007637953,0.00001065131,0.00003329384,0.001156917,0.9775658,0.000007841177,0.01153364,0.0002336924],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9973817,0.0005221177,0.0004807011,0.0002467394,0.0006215841,0.0005564985,0.00006356408,0.00001452449,0.0001126009],"genre_scores_gemma":[0.9947096,0.0009965755,0.001456188,0.002047391,0.0001491825,0.0000230764,0.00004517817,0.00004481954,0.0005279782],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.01834223,"threshold_uncertainty_score":0.9417803,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.009853692199721976,"score_gpt":0.2609067572356633,"score_spread":0.2510530650359413,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}