{"id":"W2985852902","doi":"10.1021/acs.jmedchem.9b01227","title":"Fast Iterative Synthetic Approach toward Identification of Novel Highly Selective p38 MAP Kinase Inhibitors","year":2019,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Melanoma and MAPK Pathways","field":"Biochemistry, Genetics and Molecular Biology","cited_by":27,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Eshelman Institute for Innovation, University of North Carolina at Chapel Hill; Merck Sharp and Dohme; Ontario Ministry of Research, Innovation and Science; Fundação de Amparo à Pesquisa do Estado de São Paulo; Deutsche Forschungsgemeinschaft; Deutschen Konsortium für Translationale Krebsforschung; Novartis; Ontario Genomics Institute; Canada Foundation for Innovation; Wellcome Trust; AbbVie; Takeda Pharmaceutical Company; Janssen Pharmaceuticals; Merck KGaA; Innovative Medicines Initiative; Wellcome; Bayer; Pfizer; Boehringer Ingelheim","keywords":"Chemistry; p38 mitogen-activated protein kinases; Kinase; Mitogen-activated protein kinase; Drug discovery; Potency; Small molecule; Gene isoform; Selectivity; Protein kinase A; Biochemistry; Combinatorial chemistry; Computational biology; In vitro; Pharmacology; Biology; Gene","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":[0.0004315178,0.000164634,0.0003019963,0.00004677206,0.00002553367,0.00001199052,0.000237744,0.0001775512,0.00002044205],"category_scores_gemma":[0.0001473357,0.000135197,0.0001544789,0.00009166994,0.00009188653,0.00001017617,0.00004753483,0.0002469888,0.000003440361],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00003982675,"about_ca_system_score_gemma":0.0001913174,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000002979882,"about_ca_topic_score_gemma":1.19949e-7,"domain_scores_codex":[0.9986123,0.00003207096,0.0005906562,0.000227087,0.0003703255,0.0001675937],"domain_scores_gemma":[0.9985438,0.00002111466,0.0006929083,0.0002241432,0.000395091,0.0001229309],"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":[0.0002152963,0.0002181948,0.0007826904,0.0003218587,0.00009511599,0.000006674033,0.0002630595,0.00006194266,0.9966868,0.0000151175,0.00095756,0.0003757621],"study_design_scores_gemma":[0.001129299,0.0003986631,0.0005272086,0.0001381596,0.00006473578,0.0002693316,0.0009016547,0.000109603,0.9948418,0.00001198094,0.001474116,0.0001334372],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9920364,0.0008785974,0.003880235,0.0001397796,0.0003385764,0.0001139692,0.00002079614,0.000003220584,0.002588413],"genre_scores_gemma":[0.9977837,0.00003830426,0.0005563931,0.00003844473,0.0006459327,0.000003769717,0.00003868005,0.00001599328,0.000878813],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.005747256,"threshold_uncertainty_score":0.5513173,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.009223267021268149,"score_gpt":0.230152640214313,"score_spread":0.2209293731930448,"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."}}