{"id":"W3128769516","doi":"10.1021/acs.jmedchem.0c01941","title":"Constraining the Side Chain of C-Terminal Amino Acids in Apelin-13 Greatly Increases Affinity, Modulates Signaling, and Improves the Pharmacokinetic Profile","year":2021,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Apelin-related biomedical research","field":"Medicine","cited_by":23,"is_retracted":false,"has_abstract":true,"ca_institutions":"Institute for Research in Immunology and Cancer; Université de Montréal; Université de Sherbrooke","funders":"Fonds de Recherche du Québec - Santé; Canadian Institutes of Health Research; Mitacs; Vrije Universiteit Brussel; Canada Foundation for Innovation; Université de Sherbrooke; Canada Research Chairs; Government of Canada; Heart and Stroke Foundation of Canada","keywords":"Chemistry; Pharmacokinetics; Terminal (telecommunication); Apelin; Side chain; Amino acid; Pharmacology; Biochemistry; Stereochemistry; Receptor; Organic chemistry","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":[0.001964857,0.0002130385,0.000573682,0.00008646611,0.00007719269,0.00002222417,0.0003035057,0.0001788579,0.0003359628],"category_scores_gemma":[0.003248005,0.000114278,0.0001435064,0.000378245,0.00112752,0.0000561018,0.0001584428,0.001581119,0.000001302839],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0000685232,"about_ca_system_score_gemma":0.0009600098,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0000356487,"about_ca_topic_score_gemma":0.000002929581,"domain_scores_codex":[0.9971517,0.000157223,0.0009333736,0.0002142429,0.001179768,0.0003636813],"domain_scores_gemma":[0.9971039,0.00136544,0.0004756429,0.0002294149,0.0004868222,0.0003387418],"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":[0.0005850709,0.0002470883,0.01538475,0.00058618,0.00019878,0.002229352,0.0006721462,0.000006396611,0.9600971,0.000002707413,0.0002404079,0.01975004],"study_design_scores_gemma":[0.009450945,0.001043226,0.1143963,0.004912619,0.0009547462,0.02004284,0.01361687,0.003872587,0.8306109,0.0002143451,0.0005821027,0.0003024389],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9885992,0.005927924,0.00001922851,0.004429332,0.00006333552,0.0001614173,0.000008059352,0.000006655774,0.0007848853],"genre_scores_gemma":[0.9977475,0.0007393582,0.0001953626,0.0003865954,0.0006678398,0.000005328163,0.000008916216,0.00001879262,0.000230258],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.1294861,"threshold_uncertainty_score":0.6869263,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02145228105631377,"score_gpt":0.3128564447066888,"score_spread":0.291404163650375,"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."}}