{"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":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0005650774,0.0005673877,0.0008107066,0.0001864622,0.0001172687,0.00004030059,0.0001949931,0.0002466184,0.0001143266],"category_scores_gemma":[0.0005521388,0.0005156299,0.0001234451,0.0009749391,0.0002781971,0.0001278124,0.0003131262,0.0009246637,0.0001696954],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0009638262,"about_ca_system_score_gemma":0.0003848899,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0004384639,"about_ca_topic_score_gemma":0.00005674002,"domain_scores_codex":[0.9963587,0.00006065246,0.0006695458,0.001002872,0.0008838054,0.001024404],"domain_scores_gemma":[0.9978973,0.0003545218,0.0001279196,0.00070774,0.00006922481,0.0008432608],"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":[0.0009172058,0.000216708,0.0161764,0.0007122385,0.000109763,0.004496796,0.001227439,0.000008518637,0.9211149,0.000002098915,0.05228721,0.002730716],"study_design_scores_gemma":[0.02043206,0.0004527431,0.07112211,0.001989736,0.0004598052,0.001620009,0.002093394,0.000187305,0.8831407,0.00005429355,0.01717925,0.00126861],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.969176,0.0002778285,0.000004065908,0.02881008,0.0002870685,0.000682,0.00002484432,0.0002679234,0.0004702114],"genre_scores_gemma":[0.9888026,0.00009004898,0.0002589558,0.008305964,0.001179241,0.0001559077,0.0001804462,0.0000840583,0.0009427793],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.05494571,"threshold_uncertainty_score":0.9997295,"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."}}