{"id":"W4309244403","doi":"10.1021/acs.jmedchem.2c01041","title":"Macrocyclization of Quinazoline-Based EGFR Inhibitors Leads to Exclusive Mutant Selectivity for EGFR L858R and Del19","year":2022,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Lung Cancer Treatments and Mutations","field":"Medicine","cited_by":31,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Eshelman Institute for Innovation, University of North Carolina at Chapel Hill; Argonne National Laboratory; Ontario Genomics Institute; National Institute of General Medical Sciences; Genentech; Canada Foundation for Innovation; National Institutes of Health; Ontario Genomics; Wellcome Trust; Fundação de Amparo à Pesquisa do Estado de São Paulo; Genome Canada; Bayer; National Cancer Institute; European Federation of Pharmaceutical Industries and Associations; AbbVie; Takeda Pharmaceutical Company; Janssen Pharmaceuticals; Merck KGaA; Innovative Medicines Initiative; Wellcome; Merck; Pfizer; McGill University; Boehringer Ingelheim","keywords":"Kinome; Gefitinib; Erlotinib; EGFR inhibitors; Quinazoline; Epidermal growth factor receptor; Chemistry; T790M; Erlotinib Hydrochloride; Mutant; Cancer research; Mutation; Kinase; Biology; Receptor; Biochemistry; Combinatorial chemistry; Gene","routes":{"ca_aff":false,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":true},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0001400592,0.0003207099,0.0002196574,0.0001373113,0.0001274438,0.0001678248,0.0002924647,0.0001810599,0.002254538],"category_scores_gemma":[0.0001745733,0.00008612416,0.0001656905,0.0001225004,0.0001461137,0.0001821949,0.0001966793,0.0002723805,0.0003690492],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001784155,"about_ca_system_score_gemma":0.000199644,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005447299,"about_ca_topic_score_gemma":0.001188826,"domain_scores_codex":[0.9999083,0.00001276226,0.000005850693,0.00002728965,0.00001332504,0.00003238373],"domain_scores_gemma":[0.9999506,0.00001032115,0.00001275585,0.000005074396,0.000008160777,0.00001303539],"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":[0.001070699,0.000266268,0.0003586375,0.0003615566,0.00003360235,0.000775751,0.0001156114,0.00279443,0.9729946,0.00196286,0.001243599,0.01802231],"study_design_scores_gemma":[0.0003750714,0.008583186,0.003977914,0.00006109166,0.00005351936,0.0009409828,0.00007998079,0.004712946,0.9646791,0.0004570746,0.01602639,0.00005270571],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9784896,0.002718098,0.007840168,0.0002555781,0.00008929569,0.0002303079,0.0009058809,0.0003212507,0.009149723],"genre_scores_gemma":[0.9950914,0.001274397,0.001906988,0.00009198789,0.000007891365,0.00005168288,0.0002587049,0.00001716664,0.001299625],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002254538,"threshold_uncertainty_score":0.007542193,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.009237360836169876,"score_gpt":0.3187743727602614,"score_spread":0.3095370119240916,"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."}}