{"id":"W2949252818","doi":"10.1021/jacs.9b02822","title":"Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening","year":2019,"lang":"en","type":"article","venue":"Journal of the American Chemical Society","topic":"Click Chemistry and Applications","field":"Chemistry","cited_by":342,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Medical Research Council; Genome Canada; Fundação de Amparo à Pesquisa do Estado de São Paulo; Ministry of Science and Technology, Israel; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; Wellcome Trust; Novartis Pharma; Ontario Genomics Institute; European Federation of Pharmaceutical Industries and Associations; Innovative Medicines Initiative; Wellcome; Merck KGaA; Ontario Ministry of Research, Innovation and Science; Ontario Genomics; Rising Tide Foundation; Pfizer; Israel Science Foundation; Israel Cancer Research Fund","keywords":"Chemistry; Electrophile; Covalent bond; Ligand efficiency; Combinatorial chemistry; Drug discovery; Fragment (logic); Ligand (biochemistry); Cysteine; Selectivity; Deubiquitinating enzyme; Stereochemistry; High-throughput screening; Enzyme; Biochemistry; Organic chemistry; Receptor; Gene; Ubiquitin","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":[0.001426619,0.001170935,0.0006910135,0.0006697049,0.0003511611,0.0005979565,0.0006597168,0.0005427635,0.003272665],"category_scores_gemma":[0.0009776959,0.0003243338,0.0005610251,0.0006855465,0.0004324795,0.0007193088,0.0009287462,0.000963534,0.001019763],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000506661,"about_ca_system_score_gemma":0.0003460369,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0003054205,"about_ca_topic_score_gemma":0.0009267207,"domain_scores_codex":[0.9992441,0.0001447958,0.00005344146,0.0001664879,0.000236566,0.0001546252],"domain_scores_gemma":[0.9996141,0.0001322728,0.00006972177,0.00007749711,0.00006240343,0.00004392401],"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":[0.0002040573,0.0001721337,0.0004516179,0.0001911275,0.00005388943,0.000242118,0.0000778742,0.001292787,0.9693654,0.001444889,0.0006734568,0.02583065],"study_design_scores_gemma":[0.00002680331,0.000701892,0.0004710572,0.000006873177,0.0000253651,0.0002398632,0.00001600873,0.001375179,0.9915786,0.0002436226,0.00529665,0.00001808225],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.6626824,0.006004455,0.3091849,0.0004544584,0.0001378753,0.001806626,0.002396508,0.002550772,0.01478215],"genre_scores_gemma":[0.9155945,0.004240435,0.06673543,0.0002623768,0.00003823745,0.0009125254,0.002253576,0.00019048,0.009772545],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003272665,"threshold_uncertainty_score":0.01094812,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.008438640852305347,"score_gpt":0.2361901191006167,"score_spread":0.2277514782483114,"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."}}