{"id":"W4385189274","doi":"10.1021/acs.jmedchem.3c00884","title":"Leucettinibs, a Class of DYRK/CLK Kinase Inhibitors Inspired by the Marine Sponge Natural Product Leucettamine B","year":2023,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Protein Tyrosine Phosphatases","field":"Biochemistry, Genetics and Molecular Biology","cited_by":32,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Structural Genomics Consortium; H2020 Health; Fonds Unique Interministériel; Agence Nationale de la Recherche; Eurostars; Bpifrance; Fondation Jérôme Lejeune; Horizon 2020 Framework Programme; Deutsches Krebsforschungszentrum","keywords":"DYRK1A; Natural product; Kinase; Phosphorylation; Chemistry; Cyclin-dependent kinase 1; Biochemistry; IC50; Enzyme; Protein-Tyrosine Kinases; Tyrosine kinase; Residue (chemistry); Stereochemistry; Biology; In vitro; Signal transduction; Gene; Cell cycle","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":[0.0008858181,0.0002415192,0.0003626102,0.00004762029,0.00006744188,0.00001461541,0.0005691243,0.0001272998,0.00004710518],"category_scores_gemma":[0.00136279,0.0001645251,0.0001867376,0.0003245584,0.000302669,0.00001173894,0.0002572469,0.0004759174,0.000002828475],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00004013076,"about_ca_system_score_gemma":0.0002472514,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000023542,"about_ca_topic_score_gemma":0.000003146332,"domain_scores_codex":[0.9980559,0.00005779533,0.0006955925,0.0002595029,0.000612713,0.0003185486],"domain_scores_gemma":[0.9983687,0.00005428589,0.0006760838,0.0004435809,0.0003080275,0.0001492805],"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":[0.0004308701,0.00007564144,0.0009610275,0.0001649978,0.0001039409,0.00008761397,0.00002517654,0.000008613953,0.8939853,0.000004183265,0.09658516,0.007567411],"study_design_scores_gemma":[0.001277294,0.0002935133,0.001396879,0.0001369641,0.00007112263,0.0004891736,0.0001403997,0.00001555514,0.9577087,0.00002794091,0.03828356,0.0001589147],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9778075,0.01777213,0.000009084731,0.003509216,0.0003920792,0.0001481981,0.00005546187,0.00001261117,0.0002937398],"genre_scores_gemma":[0.9961886,0.0004902427,0.0001126105,0.0002283814,0.001609801,0.000008560432,0.0002203652,0.0000303306,0.001111123],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.06372333,"threshold_uncertainty_score":0.6709139,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.006953644748059586,"score_gpt":0.2408873986309239,"score_spread":0.2339337538828643,"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."}}