{"id":"W4406495237","doi":"10.1101/2025.01.13.632834","title":"Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretion in vitro and in vivo of a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001","year":2025,"lang":"en","type":"preprint","venue":"bioRxiv (Cold Spring Harbor Laboratory)","topic":"Diabetes Treatment and Management","field":"Medicine","cited_by":2,"is_retracted":false,"has_abstract":true,"ca_institutions":"McGill University Health Centre; Université de Montréal; Health Sciences Centre; Centre Hospitalier de l’Université de Montréal","funders":"National Institute of Diabetes and Digestive and Kidney Diseases; Biotechnology and Biological Sciences Research Council; Medical Research Council; Canadian Institutes of Health Research; National Institutes of Health; Eli Lilly and Company; Society for Endocrinology; Diabetes UK; Wellcome Trust","keywords":"Internalization; In vivo; Agonist; In vitro; Kinetics; Chemistry; Receptor; Endocrinology; Internal medicine; Secretion; Insulin; Dual (grammatical number); Cell biology; Biology; Biochemistry; Medicine; Physics; Philosophy; Genetics","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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0002405126,0.0002052553,0.0001456031,0.00008259295,0.0000760765,0.0002142813,0.0001821805,0.0002644579,0.001534436],"category_scores_gemma":[0.0001635809,0.0001668049,0.0002099896,0.00008908789,0.0001171258,0.0001567601,0.00006667556,0.000490071,0.0003991438],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002041878,"about_ca_system_score_gemma":0.000105397,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0006947228,"about_ca_topic_score_gemma":0.0005192395,"domain_scores_codex":[0.9998488,0.00004061983,0.00001392543,0.00002710942,0.00003170811,0.00003777679],"domain_scores_gemma":[0.9998686,0.00005079473,0.00003272799,0.00001490829,0.0000139161,0.00001892006],"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":[0.0004448898,0.00005254477,0.00007473355,0.00002863039,0.000006404958,0.0000171897,0.00001445533,0.0001377504,0.998417,0.0000420183,0.00005582379,0.0007085962],"study_design_scores_gemma":[0.00002547135,0.001163707,0.001510728,0.00000454177,0.0000129244,0.0000851705,0.00002137786,0.001636425,0.9948236,0.00001000333,0.0006998525,0.000006204105],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9965476,0.0007201826,0.001257015,0.0000566605,0.00001697752,0.00001993772,0.0002484124,0.00002409711,0.001109046],"genre_scores_gemma":[0.9920166,0.0008505189,0.002479388,0.00008882757,0.00001331966,0.00003317747,0.0008015258,0.00002106669,0.003695592],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001534436,"threshold_uncertainty_score":0.005133212,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01413818808095474,"score_gpt":0.2285968646671334,"score_spread":0.2144586765861787,"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."}}