{"id":"W2898372019","doi":"10.1021/acs.jmedchem.8b01262","title":"Discovery and Preclinical Characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine (PQR620), a Highly Potent and Selective mTORC1/2 Inhibitor for Cancer and Neurological Disorders","year":2018,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"PI3K/AKT/mTOR signaling in cancer","field":"Biochemistry, Genetics and Molecular Biology","cited_by":85,"is_retracted":false,"has_abstract":true,"ca_institutions":"University of Victoria","funders":"Kommission für Technologie und Innovation; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; Cancer Research Society; Epilepsy Foundation","keywords":"Chemistry; In vivo; PI3K/AKT/mTOR pathway; mTORC1; Kinase; Cell growth; Cmax; Pharmacology; In vitro; Cancer research; Biochemistry; Signal transduction; Pharmacokinetics; Medicine; Biology","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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0001847451,0.0003738466,0.0001993264,0.0002047174,0.0001157125,0.0002310284,0.0002028076,0.0002133968,0.001162764],"category_scores_gemma":[0.0001090666,0.0001167463,0.0001897093,0.0001298798,0.0001401292,0.0001660344,0.0001027631,0.0003736806,0.0004350846],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000265864,"about_ca_system_score_gemma":0.0004855539,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001014229,"about_ca_topic_score_gemma":0.001793993,"domain_scores_codex":[0.9999511,0.000007664985,0.000002961926,0.000008832378,0.0000122498,0.00001715174],"domain_scores_gemma":[0.9999539,0.000002992839,0.00001214072,0.00000417706,0.000008362334,0.0000184657],"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":[0.0004847945,0.0005647279,0.0003787941,0.0001012154,0.00001781551,0.000103675,0.00003087385,0.0007319534,0.9812196,0.0002719093,0.0005594543,0.01553526],"study_design_scores_gemma":[0.0005056139,0.01531586,0.005181509,0.00001893895,0.00009721738,0.0005992992,0.00002223418,0.002049641,0.9658401,0.0001417124,0.01021363,0.00001444524],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9800538,0.005666396,0.00675738,0.0002814932,0.00005832889,0.0003908977,0.00116119,0.0001846586,0.005445862],"genre_scores_gemma":[0.9917487,0.002308614,0.001802588,0.00007846348,0.00001531961,0.00008229838,0.001081685,0.00001427589,0.002868033],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001162764,"threshold_uncertainty_score":0.003889859,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01084998520920675,"score_gpt":0.2885371264130607,"score_spread":0.2776871412038539,"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."}}