{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0004213305,0.00009828819,0.0001968482,0.00002346832,0.00002033258,0.000005312761,0.00007476498,0.0001441401,0.000019063],"category_scores_gemma":[0.0002785539,0.00008810882,0.00008593067,0.00005162828,0.0001232701,0.00002617367,0.00002594069,0.00008693211,6.822835e-8],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00002214142,"about_ca_system_score_gemma":0.00006540187,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000001185297,"about_ca_topic_score_gemma":4.973204e-8,"domain_scores_codex":[0.9989402,0.00002256235,0.0005892675,0.0001032416,0.0002240803,0.0001206396],"domain_scores_gemma":[0.9987908,0.0000174715,0.0007616951,0.000104337,0.0002460339,0.00007967722],"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":[0.0002625959,0.0001401658,0.0002233543,0.0002979117,0.0000353506,7.094529e-7,0.0001505312,0.00001536223,0.9980133,0.0000115975,0.0002947391,0.0005543437],"study_design_scores_gemma":[0.001226975,0.0001885391,0.0001144349,0.0001554799,0.00006546611,0.0002257404,0.000197429,0.0001208042,0.9973437,0.00008611203,0.0001985597,0.00007674989],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9230072,0.001022153,0.07555346,0.0001524044,0.00006678332,0.0001342754,0.00001266529,0.00000176519,0.00004924119],"genre_scores_gemma":[0.9918156,0.000122534,0.007499119,0.00002737245,0.000429391,0.000008575119,0.00005440033,0.00001035664,0.00003260539],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0688084,"threshold_uncertainty_score":0.3592973,"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."}}