{"id":"W4414908145","doi":"10.1021/acs.jmedchem.5c02248","title":"Optimization of 2,8-Diaryl-1,5-naphthyridines as <i>Plasmodium falciparum</i> Phosphatidylinositol 4-Kinase Inhibitors with Improved ADME Profiles and In Vivo Efficacy","year":2025,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Synthesis and biological activity","field":"Chemistry","cited_by":0,"is_retracted":false,"has_abstract":true,"ca_institutions":"Discovery Centre","funders":"National Institutes of Health; University of Cape Town; Medical Research Council; South African Medical Research Council; Medicines for Malaria Venture; NHLBI Division of Intramural Research; University of Sussex; National Institute of Allergy and Infectious Diseases; Division of Intramural Research, National Institute of Allergy and Infectious Diseases; Bill and Melinda Gates Foundation","keywords":"ADME; hERG; Pharmacokinetics; In vivo; Cytotoxicity; Kinase; Phosphatidylinositol; Selectivity; In vitro","routes":{"ca_aff":true,"ca_fund":false,"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":[0.0002319859,0.0004086868,0.0003289086,0.0002202518,0.00007905432,0.0002409048,0.0002718232,0.0001504971,0.001157406],"category_scores_gemma":[0.0001148099,0.0001460204,0.0001637279,0.0001851135,0.00009928509,0.0001472383,0.0001295062,0.0002885844,0.0003257475],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003257059,"about_ca_system_score_gemma":0.0002296091,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005554426,"about_ca_topic_score_gemma":0.001689831,"domain_scores_codex":[0.9999139,0.00001899812,0.000007536305,0.00001702887,0.00002337453,0.00001912056],"domain_scores_gemma":[0.9999512,0.000007621411,0.00001472609,0.000004349264,0.00001123364,0.00001080703],"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":[0.0006886031,0.0002666599,0.0001478574,0.00007739854,0.00001748964,0.00005997482,0.00001915063,0.002974915,0.9850352,0.0001564518,0.0002729096,0.01028349],"study_design_scores_gemma":[0.0002528029,0.003528731,0.001585516,0.000008764661,0.00004362649,0.000142277,0.00001158245,0.003946613,0.9855968,0.00004084738,0.004827902,0.00001450564],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9909307,0.001583289,0.003240436,0.00007966892,0.00001824276,0.0001687254,0.000581781,0.00009518459,0.003301929],"genre_scores_gemma":[0.9873888,0.001862915,0.006601524,0.00006018645,0.000008313485,0.00008985819,0.0007810973,0.00003952013,0.003167665],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001157406,"threshold_uncertainty_score":0.003871918,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.006949549512844164,"score_gpt":0.2346496543406932,"score_spread":0.2277001048278491,"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."}}