{"id":"W4389334337","doi":"10.1021/acsmedchemlett.3c00479","title":"Atypical <i>N</i>-Alkyl to <i>N</i>-Noralkoxy Switch in a Dual cSRC/BCR-ABL1 Kinase Inhibitor Improves Drug Efflux and hERG Affinity","year":2023,"lang":"en","type":"article","venue":"ACS Medicinal Chemistry Letters","topic":"Chronic Myeloid Leukemia Treatments","field":"Medicine","cited_by":4,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Georgia Research Alliance; National Institute of General Medical Sciences; Natural Sciences and Engineering Research Council of Canada; University of Georgia","keywords":"Chemistry; Bioisostere; Alkyl; hERG; ABL; Hydroxylamine; Molecular switch; Amine gas treating; Stereochemistry; Combinatorial chemistry; Efflux; Pharmacology; Piperazine; Medicinal chemistry; Biochemistry; Biology; Tyrosine kinase; Chemical synthesis; Biophysics; Molecule; In vitro; Organic chemistry; Receptor","routes":{"ca_aff":false,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":true},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0001035431,0.0001778169,0.00009898307,0.00008189738,0.00007502216,0.0001534362,0.0002410406,0.0002305149,0.003110234],"category_scores_gemma":[0.00007097722,0.00008361436,0.0000905905,0.00005974988,0.0001384926,0.0002231009,0.0001356691,0.0002737809,0.000459524],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001349045,"about_ca_system_score_gemma":0.0001098265,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0003516724,"about_ca_topic_score_gemma":0.0006513768,"domain_scores_codex":[0.9999394,0.000006101117,0.000004394881,0.00001783328,0.00001917616,0.00001304422],"domain_scores_gemma":[0.9999541,0.000008333191,0.00001686306,0.000005408489,0.00000645147,0.000008943101],"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":[0.00006119811,0.000006299415,0.00005461454,0.00001179315,0.000001582345,0.00003955866,0.000004511616,0.00003862548,0.9982297,0.0001038147,0.00006448878,0.001383889],"study_design_scores_gemma":[0.000007448903,0.0001513107,0.0004506166,0.000001045005,0.000003516526,0.0001061948,0.000006710118,0.0004448504,0.9968929,0.00002545709,0.001906999,0.000002800639],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9831789,0.0008397123,0.007627367,0.0002841947,0.00005871886,0.00002939424,0.0003124339,0.0002309321,0.007438478],"genre_scores_gemma":[0.9828131,0.000635644,0.009722739,0.00009915645,0.00001608068,0.00002116378,0.0002612467,0.00004424733,0.006386817],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003110234,"threshold_uncertainty_score":0.01040477,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01048495602493222,"score_gpt":0.254810160310718,"score_spread":0.2443252042857857,"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."}}