{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0003405785,0.0002238193,0.0005506211,0.00006084663,0.00004234627,0.00001780121,0.0002048687,0.0002311995,0.0002343261],"category_scores_gemma":[0.0006307127,0.0001457318,0.00009274534,0.000212988,0.0002048115,0.0001071179,0.00005714743,0.0003979098,1.450906e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00006580609,"about_ca_system_score_gemma":0.0002018957,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00002704524,"about_ca_topic_score_gemma":0.000001565771,"domain_scores_codex":[0.9985871,0.00002416607,0.0006465266,0.0002266247,0.0003072927,0.0002082897],"domain_scores_gemma":[0.9985426,0.0003742076,0.0006065137,0.0001500578,0.0001933623,0.0001332375],"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":[0.001893809,0.0004752069,0.02012455,0.0005981395,0.00008649696,0.00006774611,0.00005253356,0.0002822662,0.9739369,0.000002350037,0.0002772077,0.002202769],"study_design_scores_gemma":[0.002083396,0.0001434594,0.0009096917,0.001340562,0.00009707556,0.0001152821,0.0003997843,0.0005444628,0.9939206,0.00002335744,0.0002756874,0.000146671],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9950486,0.001269783,0.00005517567,0.0006545932,0.00005994097,0.00006997158,0.00001099689,0.00001125632,0.002819723],"genre_scores_gemma":[0.9986486,0.0002772282,0.0006024173,0.00005386608,0.0002083894,0.000005568792,0.000003634577,0.00001003331,0.0001902069],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.01998364,"threshold_uncertainty_score":0.5942771,"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."}}