{"id":"W4321367247","doi":"10.1021/acs.jmedchem.2c01933","title":"Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21","year":2023,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Ubiquitin and proteasome pathways","field":"Biochemistry, Genetics and Molecular Biology","cited_by":25,"is_retracted":false,"has_abstract":true,"ca_institutions":"Structural Genomics Consortium; University of Toronto","funders":"Natural Sciences and Engineering Research Council of Canada; Horizon 2020 Framework Programme; Genentech; Kungliga Tekniska Högskolan; Ontario Institute for Cancer Research; Takeda Pharmaceutical Company; European Federation of Pharmaceutical Industries and Associations; Structural Genomics Consortium; Janssen Pharmaceuticals; Merck KGaA; Genome Canada; Bayer; Bristol-Myers Squibb; European Commission; Pfizer; Diamond Light Source; McGill University; Boehringer Ingelheim","keywords":"Chemistry; Deubiquitinating enzyme; Ubiquitin; Surface plasmon resonance; Proteases; Biochemistry; High-throughput screening; Enzyme; Subfamily; Kinase; Protease; Phenotypic screening; Gene; Nanotechnology; Phenotype","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0003221882,0.0003710137,0.000380222,0.0002826985,0.0001176236,0.0003845975,0.0003143525,0.0002942311,0.0006377639],"category_scores_gemma":[0.0002294411,0.0001375238,0.0002610238,0.0002687423,0.0001622086,0.000235898,0.0001907251,0.0005421227,0.0004094966],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003890562,"about_ca_system_score_gemma":0.0004007003,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005947967,"about_ca_topic_score_gemma":0.0008582277,"domain_scores_codex":[0.9998823,0.00001430258,0.00001389825,0.00001798001,0.00004877686,0.00002268274],"domain_scores_gemma":[0.9999113,0.00001014162,0.00001989451,0.0000114293,0.00002185631,0.00002542807],"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":[0.00009076365,0.0001359453,0.0002494029,0.00005379964,0.00001297375,0.00007488034,0.00001983439,0.000445498,0.9922912,0.0001363808,0.0001292662,0.006360136],"study_design_scores_gemma":[0.0001299106,0.001693211,0.00239932,0.000008626652,0.0000647152,0.0005029759,0.00001619189,0.002872085,0.9850506,0.00008515247,0.007166275,0.00001100583],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9736573,0.007638497,0.0137169,0.0003143624,0.00003661965,0.0002222364,0.0009159454,0.0001490819,0.003349147],"genre_scores_gemma":[0.9817743,0.004209458,0.008687994,0.0001805399,0.00002221837,0.00006205598,0.001908171,0.00001968648,0.003135522],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0006377639,"threshold_uncertainty_score":0.002822816,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01047423589911737,"score_gpt":0.2313072864173327,"score_spread":0.2208330505182153,"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."}}