{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.000630117,0.0002840631,0.0005583015,0.00005717718,0.00009137877,0.00003381983,0.0001795495,0.0003401237,0.00001071168],"category_scores_gemma":[0.0007797051,0.0002288107,0.0001225422,0.0001143346,0.0006618839,0.00003398531,0.0001241005,0.0003300117,7.992058e-8],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00003851832,"about_ca_system_score_gemma":0.0002542268,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000008339064,"about_ca_topic_score_gemma":0.000006977892,"domain_scores_codex":[0.9980801,0.00007113595,0.0007466771,0.0004629762,0.0003412171,0.000297915],"domain_scores_gemma":[0.9982988,0.0001641175,0.0007417987,0.0001772659,0.0003828862,0.0002351358],"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":[0.002236458,0.0001166756,0.01073352,0.0002114864,0.0001874412,0.000005552745,0.00008612256,0.00000184562,0.979609,0.000003343328,0.000486391,0.006322223],"study_design_scores_gemma":[0.005077929,0.005603972,0.03805207,0.0003556896,0.0004191129,0.0002735217,0.0001018241,0.0001624971,0.9393699,0.0001800131,0.009964329,0.0004392061],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9930423,0.00383442,0.001182862,0.001207095,0.0003533018,0.0002362025,0.0001010576,0.000005837299,0.00003685488],"genre_scores_gemma":[0.9935098,0.003066651,0.0003960509,0.0002500417,0.00253392,0.00002098489,0.00002992042,0.0000321373,0.0001605039],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.04023911,"threshold_uncertainty_score":0.933063,"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."}}