{"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":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0003890442,0.0005874379,0.0004959742,0.0002634027,0.00007503828,0.0001270095,0.0002319262,0.0007786544,0.000005960635],"category_scores_gemma":[0.00006140847,0.000652948,0.0001586359,0.000416036,0.0001434716,0.00001211217,0.0005210654,0.0007572355,0.00001022493],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003592178,"about_ca_system_score_gemma":0.0006458234,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001331673,"about_ca_topic_score_gemma":0.00002946636,"domain_scores_codex":[0.9971883,0.0002435309,0.0003971562,0.001446122,0.0002710768,0.0004538257],"domain_scores_gemma":[0.9986724,0.00002688947,0.0001944838,0.0006586174,0.0002476349,0.0001999314],"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":[0.0001727351,0.0000999726,0.0002072766,0.0002954572,0.0003120403,0.00001927428,0.00002892308,0.001596579,0.9970883,0.00001143098,0.0001332834,0.00003476542],"study_design_scores_gemma":[0.0005175443,0.0001416965,0.0213774,0.0002780441,0.0001425639,6.31397e-8,0.000004400142,0.001179388,0.9753859,0.000008439938,0.0003065424,0.000657998],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.993183,0.003534272,0.0005722142,0.0002574676,0.0009475027,0.00105468,0.0003672463,0.00007783881,0.000005761681],"genre_scores_gemma":[0.9970891,0.001217134,0.0008921301,0.00005451957,0.0003835459,0.000223142,0.000001402683,0.0001276683,0.00001130791],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.02170234,"threshold_uncertainty_score":0.9995922,"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."}}