{"id":"W4281393985","doi":"10.1021/acs.jmedchem.2c00173","title":"Illuminating the Dark: Highly Selective Inhibition of Serine/Threonine Kinase 17A with Pyrazolo[1,5- <i>a</i> ]pyrimidine-Based Macrocycles","year":2022,"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":"Structural Genomics Consortium; Deutsche Forschungsgemeinschaft","keywords":"Kinome; Chemistry; Serine; Pyrimidine; Kinase; Programmed cell death; Protein kinase A; Threonine; Biochemistry; Cell growth; In vitro; Drug discovery; Apoptosis; Cell biology; Cancer research; Phosphorylation; Biology","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":[0.0005762218,0.0001688568,0.0002557564,0.00003556469,0.0001690318,0.00000760873,0.0002458745,0.00006742058,0.00005054012],"category_scores_gemma":[0.0001208404,0.0001149812,0.0001166306,0.0001635171,0.0001558937,0.000005854277,0.00009369377,0.00041288,1.834171e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00005369993,"about_ca_system_score_gemma":0.0003499334,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000009878989,"about_ca_topic_score_gemma":0.000004333676,"domain_scores_codex":[0.9986183,0.00006275985,0.0004218563,0.0001799122,0.0005150823,0.0002020878],"domain_scores_gemma":[0.9987143,0.00004429895,0.000653701,0.0002088971,0.0002805574,0.00009821165],"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":[0.0008362225,0.0001249034,0.0007048104,0.0001130812,0.00007223295,0.0001295912,0.0001025161,0.000689348,0.9946407,0.000007709564,0.001881857,0.0006970491],"study_design_scores_gemma":[0.001715034,0.001321341,0.0003575991,0.00009035431,0.00008813656,0.0009697523,0.001128211,0.00006023811,0.9900419,0.00003239602,0.004061451,0.0001335746],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9965201,0.0008051046,0.0003631722,0.0007548118,0.0000916525,0.00008610373,0.00002576614,0.000004834146,0.001348437],"genre_scores_gemma":[0.9987428,0.00003081773,0.0003403646,0.000258075,0.0004303305,0.00001245749,0.0000512785,0.00002061453,0.0001133171],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.004598766,"threshold_uncertainty_score":0.4688797,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.005414532205947249,"score_gpt":0.2062778087777506,"score_spread":0.2008632765718033,"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."}}