{"id":"W4200594151","doi":"10.1158/1535-7163.targ-21-p251","title":"Abstract P251: Discovery and characterization of RLY-2608: The first allosteric, mutant, and isoform-selective inhibitor of PI3Kα","year":2021,"lang":"en","type":"article","venue":"Molecular Cancer Therapeutics","topic":"Chronic Lymphocytic Leukemia Research","field":"Medicine","cited_by":5,"is_retracted":false,"has_abstract":true,"ca_institutions":"Paraza Pharma (Canada)","funders":"","keywords":"Allosteric regulation; PI3K/AKT/mTOR pathway; Mutant; Gene isoform; Kinase; Protein kinase B; P110α; Protein kinase domain; Small molecule; Chemistry; Phosphoinositide 3-kinase; Pharmacology; Biochemistry; Biology; Phosphorylation; Enzyme; Signal transduction; Gene","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":[0.0001681904,0.0004154229,0.0002431306,0.0001512446,0.0001602976,0.000251019,0.0004496058,0.0002591442,0.001153157],"category_scores_gemma":[0.0001761689,0.0001274843,0.0002209375,0.0001739991,0.000185021,0.0001549949,0.0001341798,0.000493581,0.0008073431],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0004058681,"about_ca_system_score_gemma":0.0003843254,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001250608,"about_ca_topic_score_gemma":0.000918674,"domain_scores_codex":[0.9999268,0.000006127063,0.000005246805,0.00001852605,0.00002619948,0.0000170146],"domain_scores_gemma":[0.9999397,0.000003442973,0.00001175274,0.000004475882,0.0000114324,0.00002912211],"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":[0.0002217426,0.0001489467,0.0004601117,0.0000758247,0.00001660569,0.0002893849,0.00003273394,0.002582091,0.9891972,0.0003748493,0.0008249553,0.0057756],"study_design_scores_gemma":[0.0001296826,0.00157671,0.001792115,0.00001276381,0.00003213823,0.000507127,0.0000209645,0.007353754,0.9730652,0.0001182532,0.015373,0.00001828243],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9777253,0.002887442,0.01214479,0.0002412556,0.0000572735,0.0002535351,0.001695344,0.0001918211,0.004803437],"genre_scores_gemma":[0.9765577,0.001561715,0.01022117,0.0001364933,0.00001776823,0.0001229805,0.004514811,0.00007688536,0.006790522],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001250608,"threshold_uncertainty_score":0.003857732,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01830301609038135,"score_gpt":0.2862523089146916,"score_spread":0.2679492928243102,"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."}}