{"id":"W4416018018","doi":"10.1101/2025.11.06.686927","title":"Discovery and chemical biology of CDK8 inhibitors reveals insights for kinase inhibitor development","year":2025,"lang":"","type":"preprint","venue":"bioRxiv (Cold Spring Harbor Laboratory)","topic":"Advanced Breast Cancer Therapies","field":"Medicine","cited_by":0,"is_retracted":false,"has_abstract":true,"ca_institutions":"Institute of Cancer Research","funders":"Institut National Du Cancer; National Cancer Institute; Ligue Contre le Cancer","keywords":"Kinase; Chemical biology; Mediator; Drug discovery; Cytotoxic T cell; DNA damage; Protein kinase A; Signal transduction; Toxicity","routes":{"ca_aff":true,"ca_fund":false,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0003874091,0.0004565952,0.000286836,0.0004390622,0.0002296534,0.0008379171,0.0004010765,0.0003459387,0.003331478],"category_scores_gemma":[0.0002121916,0.0002804376,0.0003120388,0.0002339595,0.000355504,0.0006407966,0.000342926,0.001090319,0.001481457],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0009064189,"about_ca_system_score_gemma":0.0005380915,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005416013,"about_ca_topic_score_gemma":0.0008554934,"domain_scores_codex":[0.9998797,0.0000175645,0.000007553921,0.00002213806,0.00004590259,0.00002711387],"domain_scores_gemma":[0.9999254,0.00001251131,0.00001658222,0.00000892994,0.00001612231,0.00002049022],"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":[0.0002672288,0.0001977283,0.0006369735,0.0003131249,0.00002898215,0.00020033,0.00004869509,0.003083891,0.9238909,0.01121423,0.002700801,0.05741717],"study_design_scores_gemma":[0.0001220624,0.0005592378,0.0006745738,0.00003462821,0.0000342986,0.0004309549,0.0000225476,0.003676167,0.9369141,0.002653902,0.05485883,0.00001867028],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.6271322,0.06784508,0.2039097,0.008292429,0.0007485033,0.001155479,0.003164897,0.00138591,0.08636577],"genre_scores_gemma":[0.8619052,0.03217025,0.07819179,0.000933111,0.0001535741,0.0002461432,0.001069961,0.0001568746,0.02517301],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003331478,"threshold_uncertainty_score":0.01114494,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01308708923810649,"score_gpt":0.2508270832582997,"score_spread":0.2377399940201932,"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."}}