{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0002450195,0.0004560424,0.0002261705,0.000231604,0.00009513609,0.0002040994,0.0002976311,0.0002301863,0.001214741],"category_scores_gemma":[0.0001118442,0.000139454,0.0001345666,0.0001687557,0.0001306108,0.0002160403,0.0002491563,0.0003688141,0.0003533985],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002854262,"about_ca_system_score_gemma":0.0001767864,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002075832,"about_ca_topic_score_gemma":0.0005215344,"domain_scores_codex":[0.9999256,0.00001227826,0.000004634604,0.00001560646,0.00001656312,0.00002522997],"domain_scores_gemma":[0.9999635,0.000004634604,0.00001099092,0.000003129551,0.000005458544,0.00001221752],"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":[0.0001827644,0.0000819282,0.00013582,0.00008987504,0.00000977231,0.00006394598,0.00002127111,0.0005559584,0.9879537,0.000935037,0.0003521597,0.009617713],"study_design_scores_gemma":[0.000113024,0.0009168478,0.0008860735,0.000008329019,0.00001788418,0.0002395829,0.00000982138,0.002162792,0.9878708,0.0001339119,0.007629866,0.0000111189],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9657858,0.007569565,0.01706557,0.0003002762,0.00007508759,0.0001662029,0.0006166041,0.0003037665,0.008117002],"genre_scores_gemma":[0.9876666,0.002621339,0.006029155,0.0001219594,0.00002335887,0.00006838574,0.0002465725,0.00001824304,0.003204336],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001214741,"threshold_uncertainty_score":0.004063725,"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."}}