{"id":"W4402962108","doi":"10.1101/2024.09.27.615363","title":"Potent and Selective SETDB1 Covalent Negative Allosteric Modulator Reduces Methyltransferase Activity in Cells","year":2024,"lang":"en","type":"preprint","venue":"bioRxiv (Cold Spring Harbor Laboratory)","topic":"Cancer-related gene regulation","field":"Biochemistry, Genetics and Molecular Biology","cited_by":2,"is_retracted":false,"has_abstract":true,"ca_institutions":"Structural Genomics Consortium; University of Toronto","funders":"National Institute of General Medical Sciences; Canadian Institutes of Health Research; Genentech; Ontario Genomics Institute; National Cancer Institute; European Federation of Pharmaceutical Industries and Associations; Merck KGaA; National Institutes of Health; Ontario Genomics; Genome Canada; McGill University; Pharmaceutical Research and Manufacturers of America Foundation; Bayer; Bristol-Myers Squibb; Natural Sciences and Engineering Research Council of Canada; Canadian Light Source; Pfizer","keywords":"Allosteric regulation; Allosteric modulator; Methyltransferase; Chemistry; Covalent bond; Biophysics; Enzyme; Biochemistry; Biology; Methylation; DNA","routes":{"ca_aff":true,"ca_fund":true,"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":[0.0001524354,0.0002298242,0.0002727723,0.00009439112,0.0001134576,0.000208815,0.0002888209,0.0002398311,0.002116649],"category_scores_gemma":[0.0001669241,0.0001046792,0.0001487334,0.0001349063,0.000186008,0.00009634328,0.0001987504,0.000402235,0.0003601178],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002640991,"about_ca_system_score_gemma":0.0001477239,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0006277571,"about_ca_topic_score_gemma":0.001071233,"domain_scores_codex":[0.9998686,0.00002518877,0.000009694519,0.00002572429,0.00004528206,0.00002549281],"domain_scores_gemma":[0.9999294,0.0000269564,0.00001064969,0.00001520527,0.000007397028,0.00001039792],"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":[0.00008544004,0.00002378402,0.00009239011,0.00002285429,0.000004323658,0.00001784354,0.000009214308,0.0001274376,0.9983546,0.00008534867,0.00008611895,0.001090683],"study_design_scores_gemma":[0.000005596853,0.00007073854,0.0003447554,0.000001120651,0.000002726957,0.00003050666,0.000004208669,0.0003116158,0.9985091,0.0000106198,0.000707956,0.000001099748],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9884292,0.001712563,0.00534451,0.0001689255,0.00004316928,0.00003356891,0.0004970637,0.0002084802,0.003562579],"genre_scores_gemma":[0.9940089,0.000466636,0.002321293,0.00006807139,0.000005468002,0.00002746126,0.000352488,0.00002346378,0.002726279],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002116649,"threshold_uncertainty_score":0.007080913,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.008229620519616754,"score_gpt":0.2226465830668938,"score_spread":0.214416962547277,"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."}}