{"id":"W2804911666","doi":"10.1016/j.bmc.2018.05.003","title":"BET bromodomain ligands: Probing the WPF shelf to improve BRD4 bromodomain affinity and metabolic stability","year":2018,"lang":"en","type":"article","venue":"Bioorganic & Medicinal Chemistry","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":26,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Eshelman Institute for Innovation, University of North Carolina at Chapel Hill; Janssen Pharmaceuticals; Horizon 2020; Lady Margaret Hall, University of Oxford; Engineering and Physical Sciences Research Council; Janssen Biotech; Medical Research Council; Defence Science and Technology Laboratory; Innovative Medicines Initiative; Syngenta International; Chinesisch-Deutsche Zentrum für Wissenschaftsförderung; Biotechnology and Biological Sciences Research Council; Wellcome Trust; Cancer Research UK; Canada Foundation for Innovation; Merck; Ontario Ministry of Economic Development and Innovation; Genome Canada; Diamond Light Source; School of Public Health, University of California Berkeley; Vertex Pharmaceuticals; AstraZeneca; Fundação de Amparo à Pesquisa do Estado de São Paulo; AbbVie; Deutsche Forschungsgemeinschaft; GlaxoSmithKline; Bayer; Takeda Pharmaceuticals U.S.A.; Pfizer; Novartis Pharmaceuticals UK Limited; Boehringer Ingelheim","keywords":"Bromodomain; Chemistry; BRD4; Ligand (biochemistry); Small molecule; Stereochemistry; Histone; Biochemistry; Combinatorial chemistry; Receptor; 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":[0.0008900005,0.0003006716,0.0002887897,0.00002170493,0.0002742542,0.00005443315,0.0004148064,0.0002489084,0.0001999882],"category_scores_gemma":[0.0007578349,0.000223585,0.00008211891,0.0002244608,0.0004903716,0.000009932832,0.0003463263,0.0002417821,0.00002172795],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00003829165,"about_ca_system_score_gemma":0.0002090048,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00004761653,"about_ca_topic_score_gemma":0.00002763815,"domain_scores_codex":[0.9981354,0.0000692435,0.0003773609,0.0006785755,0.000313451,0.0004259284],"domain_scores_gemma":[0.9986249,0.00003504189,0.000136046,0.0007398309,0.0001531442,0.0003110364],"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":[0.00009440297,0.0000549724,0.0004045872,0.00004916977,0.00004608653,0.00000202483,0.0002443017,3.464002e-8,0.9952511,0.00002123275,0.002122367,0.001709729],"study_design_scores_gemma":[0.0006700917,0.0002439378,0.00129291,0.00003570003,0.00004626778,0.0000506249,0.0004444496,0.000008277134,0.9766157,0.00009226983,0.02023149,0.00026824],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9948574,0.001190684,0.0005542058,0.001642244,0.0002127752,0.000434614,0.00004387863,0.00004171381,0.001022433],"genre_scores_gemma":[0.9965266,0.00007423254,0.0003394175,0.0009050068,0.001612081,0.00004551047,0.0000563714,0.0000353276,0.0004054577],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.01863535,"threshold_uncertainty_score":0.9117531,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01004918979137563,"score_gpt":0.2329902008788434,"score_spread":0.2229410110874678,"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."}}