{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0001141066,0.0001376954,0.0002797522,0.00004617829,0.00005117825,0.00002803576,0.0000694632,0.00008799921,0.00002051602],"category_scores_gemma":[0.00001942623,0.0001011022,0.00005872191,0.0002343528,0.0002382391,0.00009302518,0.00009076457,0.0001481242,4.606558e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0006273754,"about_ca_system_score_gemma":0.001451195,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001550422,"about_ca_topic_score_gemma":0.00005300323,"domain_scores_codex":[0.9989504,0.00003294,0.0002626398,0.0002266525,0.0003289133,0.0001984218],"domain_scores_gemma":[0.9992531,0.0000679529,0.0001336704,0.000286609,0.0002100294,0.00004863448],"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":[0.0002951379,0.00008601677,0.002042944,0.0004144546,0.0003443586,0.00005168777,0.001125347,0.000005215426,0.9877458,0.00009768742,0.000004856612,0.007786471],"study_design_scores_gemma":[0.003850468,0.0001973388,0.04898389,0.000272306,0.0002103194,0.00009268783,0.0001638187,0.001030278,0.9431531,0.00008130939,0.00184113,0.0001233873],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9942842,0.003486115,0.0003673036,0.001218892,0.00006495824,0.0003304279,0.00004356685,0.00000765322,0.0001969285],"genre_scores_gemma":[0.995927,0.00306473,0.00004325411,0.0007512737,0.00005317104,0.00002251384,0.00002104579,0.00002862576,0.0000884327],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.04694095,"threshold_uncertainty_score":0.412283,"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."}}