{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0002565799,0.0007264256,0.0005397759,0.000328839,0.0001921221,0.0004834139,0.0004883345,0.0002975301,0.001664318],"category_scores_gemma":[0.000160014,0.0003345818,0.0003541867,0.0003804075,0.0002561427,0.0005379697,0.0004911848,0.00070662,0.0006391707],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0007226942,"about_ca_system_score_gemma":0.0003530754,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0004375579,"about_ca_topic_score_gemma":0.001330065,"domain_scores_codex":[0.9998572,0.000015454,0.000007949549,0.00004101011,0.00004048955,0.00003786873],"domain_scores_gemma":[0.9999655,0.00000518865,0.00001218459,0.000003161333,0.00000516714,0.000008849081],"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":[0.0004910838,0.0005342145,0.0003906347,0.0004865883,0.00008038725,0.0002507326,0.00007094299,0.02342803,0.9140834,0.00698041,0.001449588,0.05175393],"study_design_scores_gemma":[0.0003673658,0.001619021,0.0005752349,0.00001904703,0.00008239039,0.0002864581,0.00003041141,0.03489709,0.9430463,0.0007997436,0.01822618,0.00005078084],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.8436641,0.006480834,0.1248904,0.0005476265,0.0001228812,0.0007251718,0.0009637155,0.001235552,0.02136967],"genre_scores_gemma":[0.9298891,0.004537621,0.05727859,0.000249361,0.00002161509,0.0003885627,0.0006277573,0.0001398823,0.006867503],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001664318,"threshold_uncertainty_score":0.00556767,"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."}}