{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.005551269,0.0002759363,0.0004435741,0.00009647726,0.0001024707,0.00002471725,0.0004216355,0.00008222804,0.0000119613],"category_scores_gemma":[0.0003454923,0.0002129913,0.0001802224,0.0001880678,0.0001951402,0.00001325002,0.00009636947,0.0004751465,0.000002805911],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001068157,"about_ca_system_score_gemma":0.0002587854,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00000731958,"about_ca_topic_score_gemma":0.000001365383,"domain_scores_codex":[0.9967711,0.0005962517,0.001412263,0.0003352649,0.0006115214,0.0002735902],"domain_scores_gemma":[0.9975449,0.0001014521,0.001357103,0.0003838151,0.0004945581,0.000118102],"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":[0.0003689552,0.0001873226,0.003350681,0.0003539701,0.00007863491,0.00008668131,0.000392674,0.005052414,0.9896163,0.000001578678,0.00009714866,0.0004136076],"study_design_scores_gemma":[0.002812542,0.0004263073,0.002829205,0.0002225703,0.0001053218,0.0000151597,0.002425107,0.0002594901,0.9890409,0.00002208248,0.001628633,0.0002126875],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.976135,0.01710339,0.004423962,0.000223866,0.0003704515,0.0002410341,0.00001147543,0.000005562452,0.001485282],"genre_scores_gemma":[0.996596,0.0009411143,0.001772669,0.00005968744,0.0004054989,0.000003435145,0.00009079229,0.00003937835,0.00009136349],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.02046109,"threshold_uncertainty_score":0.8685533,"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."}}