{"id":"W2096783705","doi":"10.1021/jm3010515","title":"Identification of a Chemical Probe for Bromo and Extra C-Terminal Bromodomain Inhibition through Optimization of a Fragment-Derived Hit","year":2012,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":196,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Wellcome Trust; Canadian Institutes of Health Research; Genome Canada; Novartis Foundation; GlaxoSmithKline; Ontario Ministry of Research and Innovation; Pfizer; Eli Lilly and Company","keywords":"Bromodomain; Acetylation; Histone Acetyltransferases; Chemistry; Histone; BRD4; Small molecule; Epigenetics; Chromatin; Biochemistry; Histone acetyltransferase; Lysine; Structure–activity relationship; Computational biology; In vitro; Amino acid; DNA; Biology; 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":[0.0002971522,0.000451698,0.0003454456,0.000318389,0.000178776,0.0002547411,0.0005139193,0.0003947929,0.001672129],"category_scores_gemma":[0.000253944,0.0001788183,0.000297942,0.0002357406,0.0002655089,0.0002258483,0.0002707465,0.0006856589,0.0003409232],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000426232,"about_ca_system_score_gemma":0.0004031038,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0006372799,"about_ca_topic_score_gemma":0.001460064,"domain_scores_codex":[0.9998415,0.00002527218,0.000008325929,0.00003128362,0.0000493038,0.00004422654],"domain_scores_gemma":[0.9998988,0.00002471979,0.0000271737,0.000009350219,0.00001760855,0.00002228438],"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":[0.0003005523,0.000189213,0.0002002954,0.00009251763,0.00002209233,0.0001942271,0.00003984127,0.002235807,0.9872809,0.0008073873,0.0001743627,0.008462694],"study_design_scores_gemma":[0.0001978713,0.002934609,0.0007765517,0.000008035919,0.00004212372,0.0004055127,0.00001985416,0.002131571,0.9893107,0.0001593097,0.003998928,0.00001493875],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9490367,0.003365718,0.03818412,0.0004166595,0.00006639878,0.0005824358,0.0008538087,0.0002404622,0.007253797],"genre_scores_gemma":[0.9803541,0.002142751,0.01360672,0.0001800993,0.00001773421,0.0001437916,0.0005982782,0.00002206702,0.002934468],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001672129,"threshold_uncertainty_score":0.005593777,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01162130374228581,"score_gpt":0.2608740894839077,"score_spread":0.2492527857416219,"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."}}