{"id":"W4319843503","doi":"10.1002/ange.202217532","title":"Discovery of Potent and Exquisitely Selective Inhibitors of Kinase CK1 with Tunable Isoform Selectivity","year":2023,"lang":"en","type":"article","venue":"Angewandte Chemie","topic":"Protein Kinase Regulation and GTPase Signaling","field":"Biochemistry, Genetics and Molecular Biology","cited_by":3,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Grantová Agentura České Republiky; Ministerstvo Školství, Mládeže a Tělovýchovy; Deutsche Forschungsgemeinschaft; Ontario Genomics Institute; CALIPSOplus; European Federation of Pharmaceutical Industries and Associations; Merck KGaA; Ontario Genomics; Genome Canada; McGill University; Bayer; Genentech; Bader Philanthropies; Pfizer; Bristol-Myers Squibb","keywords":"Casein kinase 1; Pharmacophore; Chemistry; Kinase; Biochemistry; In vitro; Quinazoline; Selectivity; In vivo; Gene isoform; Protein kinase A; Stereochemistry; Biology; Gene; Genetics","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":[],"consensus_categories":[],"category_scores_codex":[0.0001542091,0.0001230828,0.0001742623,0.00006355464,0.00004462498,0.000009942943,0.00005380988,0.00008838342,0.000002246372],"category_scores_gemma":[0.00004318667,0.0001040427,0.00005319158,0.0003014477,0.0001043894,0.00001285734,0.00007370417,0.00005513203,6.408766e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00001304188,"about_ca_system_score_gemma":0.00007320396,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00005030203,"about_ca_topic_score_gemma":0.00002039766,"domain_scores_codex":[0.9992806,0.00001567603,0.0001553317,0.0002381857,0.0001346905,0.0001754955],"domain_scores_gemma":[0.9995525,0.00001326317,0.0001152061,0.0001595818,0.0001160554,0.00004332658],"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":[0.0001732986,0.00004270761,0.00383645,0.00009493231,0.00005606554,0.000003690729,0.00007760028,0.00004219587,0.9947698,0.00003322299,0.0003659105,0.0005041111],"study_design_scores_gemma":[0.0005170506,0.0002620131,0.004941903,0.00005474451,0.00002274087,0.000007691967,0.00008962171,0.00001406789,0.9934978,0.00009969399,0.0003643054,0.0001283255],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9981679,0.0005355137,0.0002891869,0.00004206974,0.00001640754,0.000162032,0.00002968127,0.00001485798,0.0007423701],"genre_scores_gemma":[0.9991701,0.000104549,0.0001520418,0.00002462316,0.0000578029,0.00001565044,0.0000790558,0.00001618686,0.0003799699],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001271972,"threshold_uncertainty_score":0.4242736,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.009229788098629703,"score_gpt":0.2258382649656906,"score_spread":0.2166084768670609,"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."}}