{"id":"W4391401640","doi":"10.1021/acschembio.3c00427","title":"Development of Potent Dual BET/HDAC Inhibitors via Pharmacophore Merging and Structure-Guided Optimization","year":2024,"lang":"en","type":"article","venue":"ACS Chemical Biology","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":17,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Universität Duisburg-Essen; Genentech; Deutsche Krebshilfe; Bundesministerium für Bildung und Forschung; Deutschen Konsortium für Translationale Krebsforschung; Ontario Genomics Institute; European Federation of Pharmaceutical Industries and Associations; Ontario Genomics; Genome Canada; McGill University; Bayer; Pfizer; Deutsche Forschungsgemeinschaft; Deutsches Krebsforschungszentrum; Bristol-Myers Squibb","keywords":"Bromodomain; Pharmacophore; BRD4; Pancreatic cancer; Small molecule; Chemistry; Acetylation; Histone; Histone deacetylase; HDAC1; Cancer research; Biochemistry; Biology; Computational biology; Cancer; Genetics; 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":[0.000094792,0.0001483199,0.0001445549,0.00005503988,0.00003897869,0.00001187787,0.0000804427,0.0002105371,0.00003093731],"category_scores_gemma":[0.00004973975,0.0001271199,0.00004022407,0.000110521,0.0001157595,0.000005199244,0.0001497059,0.00009976381,0.000002036568],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00001862797,"about_ca_system_score_gemma":0.00006600343,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000003233313,"about_ca_topic_score_gemma":8.078941e-7,"domain_scores_codex":[0.9990661,0.00002839488,0.0003184867,0.0003414628,0.00007077102,0.0001748267],"domain_scores_gemma":[0.9996948,0.00001118218,0.00005995215,0.0001110235,0.00005258621,0.00007045487],"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":[0.00002059757,0.00001312288,0.00007832619,0.00003220898,0.00005438312,0.000001030532,0.00005640516,0.00003313511,0.9678783,0.00006707323,0.0007154942,0.03104986],"study_design_scores_gemma":[0.0002529248,0.00003647949,0.00001748409,0.00001781772,0.00001399955,0.00002062368,0.00001519791,0.0004702284,0.9856879,0.00007029275,0.01325032,0.0001467043],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9928519,0.001674852,0.004678668,0.0002025802,0.0002933493,0.0001361268,0.00002119034,0.00002478749,0.0001165846],"genre_scores_gemma":[0.9870067,0.0001190869,0.01196625,0.0001278404,0.0002270097,0.0000111324,0.0005007285,0.00001589618,0.00002538483],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.03090315,"threshold_uncertainty_score":0.51838,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.009983013576563246,"score_gpt":0.2662399040619237,"score_spread":0.2562568904853605,"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."}}