{"id":"W4312113259","doi":"10.1021/acs.jmedchem.2c01421","title":"Discovery of High-Affinity Small-Molecule Binders of the Epigenetic Reader YEATS4","year":2022,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":19,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"European Federation of Pharmaceutical Industries and Associations; McGill University; H2020 Societal Challenges; Pfizer","keywords":"Chemistry; Small molecule; Epigenetics; Acetylation; In vivo; Potency; Lysine; Molecule; In vitro; Selectivity; Structure–activity relationship; Computational biology; Stereochemistry; Förster resonance energy transfer; Biophysics; Combinatorial chemistry; Nanotechnology; Biochemistry; Fluorescence; Gene; Genetics; Amino acid; Organic chemistry; 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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0003755218,0.00009800646,0.0002009701,0.0000253222,0.00005660488,0.000004031653,0.0004003383,0.00006852682,0.00008362734],"category_scores_gemma":[0.0002442554,0.0000711267,0.0001776061,0.0001234984,0.0001638226,0.000003819669,0.0001645814,0.0002728617,1.510749e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00002858369,"about_ca_system_score_gemma":0.0003067294,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00001684745,"about_ca_topic_score_gemma":0.000001460716,"domain_scores_codex":[0.9988267,0.00007613733,0.0004491638,0.0001128272,0.000420594,0.0001146082],"domain_scores_gemma":[0.9989142,0.00001861333,0.0006262361,0.0002663904,0.0001227442,0.00005178545],"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":[0.0001461744,0.0001016286,0.001042265,0.00006082564,0.00006538963,0.000005138416,0.00004260982,0.00008178855,0.9959726,0.000008079512,0.002242956,0.0002304983],"study_design_scores_gemma":[0.0006827303,0.000269422,0.001417517,0.0000467055,0.00004783271,0.0001140221,0.0005683049,0.000003092905,0.9951847,0.00005214989,0.001543619,0.00006993073],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9972026,0.001079766,0.0002234454,0.0005619875,0.000238302,0.00005745664,0.00001746313,0.000001093861,0.0006179298],"genre_scores_gemma":[0.9987257,0.00008235051,0.000105275,0.0001416922,0.0002282523,0.000002764161,0.00001117735,0.0000104726,0.0006922904],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.00152317,"threshold_uncertainty_score":0.2900462,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01025664589363532,"score_gpt":0.2208825905011442,"score_spread":0.2106259446075089,"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."}}