{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0002216699,0.0002669872,0.0002252943,0.000108357,0.0001261784,0.0002198083,0.0003149675,0.0002621776,0.001901633],"category_scores_gemma":[0.000223628,0.0001223844,0.0001833923,0.00009893267,0.0001488751,0.0003304755,0.0002153086,0.0004038171,0.0003508516],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003787845,"about_ca_system_score_gemma":0.0001424782,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0004890108,"about_ca_topic_score_gemma":0.0006278363,"domain_scores_codex":[0.9999105,0.00001537425,0.000004481774,0.00001437409,0.00003162421,0.00002359418],"domain_scores_gemma":[0.9999604,0.00001019011,0.0000115742,0.000003183214,0.000006634939,0.000008012657],"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":[0.0002949489,0.00007018785,0.0003123143,0.00008897147,0.00001140184,0.00005694657,0.00002480983,0.001589168,0.9890743,0.0003365677,0.0001875866,0.007952786],"study_design_scores_gemma":[0.00004379978,0.0005167937,0.0005471632,0.00000559724,0.00001057937,0.0001588061,0.00001701262,0.002956623,0.9919788,0.00008592189,0.00366987,0.000009114108],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9861802,0.003426971,0.00733123,0.0002126339,0.00002206271,0.00004238564,0.0002300141,0.00008690551,0.002467564],"genre_scores_gemma":[0.9891584,0.001558058,0.006242104,0.0001047921,0.000006066347,0.00003138229,0.0003498643,0.0000194398,0.002529951],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001901633,"threshold_uncertainty_score":0.006361604,"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."}}