{"id":"W4385383015","doi":"10.1016/j.apsb.2023.07.022","title":"A unique binding pocket induced by a noncanonical SAH mimic to develop potent and selective PRMT inhibitors","year":2023,"lang":"en","type":"article","venue":"Acta Pharmaceutica Sinica B","topic":"Cancer-related gene regulation","field":"Biochemistry, Genetics and Molecular Biology","cited_by":9,"is_retracted":false,"has_abstract":true,"ca_institutions":"Structural Genomics Consortium; University of Toronto","funders":"Natural Sciences and Engineering Research Council of Canada; Ontario Genomics; National Institutes of Health; Ontario Ministry of Research, Innovation and Science; Fundação de Amparo à Pesquisa do Estado de São Paulo; Genome Canada; Novartis Pharma; Ontario Genomics Institute; European Federation of Pharmaceutical Industries and Associations; Merck KGaA; Purdue University Center for Cancer Research; Purdue University; Pfizer","keywords":"Moiety; Guanidine; Chemistry; Binding site; Stereochemistry; Plasma protein binding; Substrate (aquarium); Drug discovery; Biochemistry; Cofactor; Selectivity; Enzyme; Combinatorial chemistry; Biology","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":[0.0001468461,0.0002721832,0.0003280171,0.00007249134,0.0001059558,0.0001607666,0.0002607164,0.0002433481,0.0007984891],"category_scores_gemma":[0.0001364709,0.0001227892,0.0001584651,0.00009173415,0.000197725,0.0002196028,0.0002987823,0.00055027,0.0003484479],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001770329,"about_ca_system_score_gemma":0.0001949298,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002327754,"about_ca_topic_score_gemma":0.0003760578,"domain_scores_codex":[0.999918,0.0000159188,0.000006524774,0.00001856473,0.00002071432,0.00002020971],"domain_scores_gemma":[0.9999576,0.000006542734,0.00001344454,0.000005877254,0.000006036976,0.00001042541],"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":[0.0001228301,0.0000170642,0.0001417422,0.00006105465,0.000005367122,0.0001200103,0.00001699021,0.0003930438,0.9957546,0.0003811576,0.00005458907,0.002931578],"study_design_scores_gemma":[0.00003568333,0.0004285399,0.0003367939,0.000003996852,0.000008744719,0.0003724668,0.00001051372,0.001199977,0.9943159,0.00009155637,0.003190216,0.000005493864],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9705659,0.003313875,0.02193011,0.0001975998,0.0000458357,0.0001081374,0.0002116876,0.0002580555,0.003368723],"genre_scores_gemma":[0.9909223,0.0008027881,0.007021689,0.0000662383,0.000007306681,0.00002508685,0.0001452925,0.00001774336,0.000991501],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0007984891,"threshold_uncertainty_score":0.002671242,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02592225153734554,"score_gpt":0.3295512584941703,"score_spread":0.3036290069568247,"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."}}