{"id":"W2343608145","doi":"10.1021/acs.jmedchem.6b00012","title":"Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit","year":2016,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":110,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Structural Genomics Consortium; Canadian Institutes of Health Research; National Cancer Institute; National Institutes of Health; Ministero dello Sviluppo Economico; Wellcome Trust; National Institute of General Medical Sciences; Wellcome","keywords":"Bromodomain; Chemistry; BRD4; Lysine; Histone; Chromatin; Acetylation; Biochemistry; Structure–activity relationship; Phenotypic screening; In vitro; Small molecule; Computational biology; Stereochemistry; Phenotype; Amino acid; Gene; Biology","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":[0.0002174312,0.0003780516,0.0002969806,0.0002192961,0.0001907904,0.0001949849,0.0003915152,0.0002673196,0.001633908],"category_scores_gemma":[0.0001734603,0.0001360328,0.0002389462,0.0001895885,0.0002149453,0.0001521749,0.0001939012,0.0005761613,0.0003296847],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003523746,"about_ca_system_score_gemma":0.0003163883,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0007747071,"about_ca_topic_score_gemma":0.001477,"domain_scores_codex":[0.9998734,0.0000214006,0.000006075927,0.00002526562,0.0000356875,0.00003819855],"domain_scores_gemma":[0.9999193,0.00001869657,0.00001754924,0.00000942062,0.00001552254,0.000019534],"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":[0.000228134,0.00007990422,0.0001927278,0.00005937371,0.00001326555,0.0001335197,0.00003547991,0.0006556405,0.9928617,0.0002834093,0.0001156469,0.005341273],"study_design_scores_gemma":[0.0001172835,0.002014374,0.001059236,0.00000598451,0.00003146845,0.0005837696,0.00002405551,0.0008401898,0.9906737,0.00009413767,0.004544514,0.0000113575],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9673297,0.002399823,0.02294474,0.0002208031,0.00003375293,0.0003497395,0.0006580545,0.0001725891,0.005890721],"genre_scores_gemma":[0.9849727,0.001686052,0.01013318,0.0001250111,0.00001298208,0.0001065428,0.0005315454,0.00002008603,0.002411774],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001633908,"threshold_uncertainty_score":0.005465984,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01061622544372781,"score_gpt":0.2585532514008763,"score_spread":0.2479370259571485,"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."}}