{"id":"W4231360843","doi":"10.1021/acs.jmedchem.9b00525","title":"(<i>S</i>)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530), a Potent, Orally Bioavailable, and Brain-Penetrable Dual Inhibitor of Class I PI3K and mTOR Kinase","year":2019,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"PI3K/AKT/mTOR signaling in cancer","field":"Biochemistry, Genetics and Molecular Biology","cited_by":55,"is_retracted":false,"has_abstract":true,"ca_institutions":"University of Victoria","funders":"H2020 Marie Skłodowska-Curie Actions; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; Cancer Research Society","keywords":"Chemistry; Morpholino; Bioavailability; Amine gas treating; Oral administration; Pharmacology; Orally active; Stereochemistry; Biochemistry; In vitro; Organic chemistry; Zebrafish","routes":{"ca_aff":true,"ca_fund":true,"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":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.001548987,0.0004970496,0.0009441774,0.0001627238,0.00007880195,0.00005038538,0.0004288667,0.0004949272,0.0002741945],"category_scores_gemma":[0.0008078355,0.0004384937,0.000244481,0.0002875784,0.0004676537,0.00003579337,0.0002494257,0.0007109543,0.000006165167],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00008773151,"about_ca_system_score_gemma":0.0005514665,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00003906595,"about_ca_topic_score_gemma":0.000003179703,"domain_scores_codex":[0.9966349,0.0001176199,0.001205076,0.0006226135,0.0008604739,0.0005592888],"domain_scores_gemma":[0.9969698,0.0002060594,0.001124909,0.0005450855,0.0006058413,0.0005483015],"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":[0.001086123,0.0001617286,0.003838374,0.000516973,0.0002649947,0.00016972,0.00006942023,0.00002919492,0.9824852,0.000003275367,0.009841312,0.001533655],"study_design_scores_gemma":[0.005255487,0.001799158,0.0009995329,0.000493373,0.0002160488,0.001998018,0.0003037121,0.00004292868,0.9601978,0.00004738832,0.02818458,0.0004619527],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9806126,0.01689516,0.00009916794,0.0008129711,0.0006101181,0.0002224663,0.0000867437,0.0000104804,0.0006503406],"genre_scores_gemma":[0.9926406,0.001573594,0.001701716,0.0005569697,0.00164625,0.000006235939,0.00004077301,0.00007283896,0.001761046],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.02228741,"threshold_uncertainty_score":0.9998067,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.006611390262523066,"score_gpt":0.234158558409189,"score_spread":0.2275471681466659,"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."}}