title: EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance.
abstract: The third-generation tyrosine kinase inhibitors (TKI), AZD9291 (osimertinib) and CO-1686 (rociletinib) of epidermal growth factor receptor (EGFR) are highly active against T790M positive non-small cell lung cancer (NSCLC). However, resistance develops rapidly. EGFR C797S mutation was reported to be a leading mechanism of resistance to the third-generation inhibitors. The C797S mutation appears to be an ideal target for overcoming the acquired resistance to the third-generation inhibitors. This review summarizes the latest development on the discovery of a fourth-generation EGFR TKI, EAI045.3.
authors.affiliation: The Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing, China.
authors.forename: Shuhang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Henan Cancer Hospital and the Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Song
authors.affiliation: Henan Cancer Hospital and the Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, China. Electronic address: delong_liu@nymc.edu.
authors.forename: Delong
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044482:Benzeneacetamides / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D044482:Benzeneacetamides; C000608614:EAI045; D047428:Protein Kinase Inhibitors; D013844:Thiazoles; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: AZD9291; EAI045; EGFR; NSCLC; Rociletinib; TKI; epidermal growth factor receptor; non-small cell lung cancer; tyrosine kinase inhibitor