{"id":"W2945911027","doi":"10.1016/j.ejmech.2019.05.041","title":"C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays","year":2019,"lang":"en","type":"article","venue":"European Journal of Medicinal Chemistry","topic":"Epigenetics and DNA Methylation","field":"Biochemistry, Genetics and Molecular Biology","cited_by":17,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Novartis Pharma; Ministero dello Sviluppo Economico; Cancer Research UK; Ontario Ministry of Economic Development and Innovation; National Institute for Health and Care Research; Diamond Light Source; Wellcome Trust; European Federation of Pharmaceutical Industries and Associations; Avon Foundation for Women; Merck KGaA; Fundação de Amparo à Pesquisa do Estado de São Paulo; Genome Canada; Royal Marsden NHS Foundation Trust; Pfizer","keywords":"Chemistry; Subfamily; Demethylase; Histone; Stereochemistry; Acetylation; Enzyme; Lysine; Biochemistry; Substituent; Amino acid","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":[0.0001556567,0.0003633493,0.0002954023,0.0001376428,0.0001109906,0.0001419488,0.0003642364,0.0002348105,0.001280593],"category_scores_gemma":[0.0001481502,0.0001487124,0.0001508727,0.0001694065,0.0001538564,0.0001650695,0.0001238703,0.000427732,0.0004375519],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003232349,"about_ca_system_score_gemma":0.0002132925,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005185498,"about_ca_topic_score_gemma":0.00121571,"domain_scores_codex":[0.9999108,0.00001603521,0.000006919177,0.00002058145,0.0000218303,0.00002383953],"domain_scores_gemma":[0.9999396,0.00001169834,0.00001799583,0.000006911191,0.00001143253,0.00001235139],"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":[0.0003286228,0.000121896,0.000183557,0.0001725994,0.00001093629,0.0001209129,0.00003903458,0.0008808545,0.99154,0.0003305079,0.0001391828,0.006131825],"study_design_scores_gemma":[0.0001090847,0.00214179,0.00116915,0.000008547712,0.00002590191,0.0003644131,0.00002163276,0.001160213,0.9880827,0.00007920083,0.006823185,0.00001410708],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9850292,0.003059684,0.005751906,0.00009992936,0.00003269982,0.0001924602,0.0006199681,0.0001119273,0.005102204],"genre_scores_gemma":[0.987538,0.002338796,0.006608909,0.0000707957,0.000008119358,0.0001050747,0.0005519202,0.00001972369,0.002758735],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001280593,"threshold_uncertainty_score":0.004284024,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02569929085634743,"score_gpt":0.278359716301801,"score_spread":0.2526604254454536,"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."}}