Naquotinib (ASP8273) is a third-generation tyrosine kinase inhibitor primarily developed for the treatment of non-small cell lung cancer (NSCLC) with specific epidermal growth factor receptor (EGFR) mutations. It shows potent activity against both activating EGFR mutations and the T790M resistance mutation, which often develops after first-line EGFR inhibitor therapy. Due to its selective inhibition profile, Naquotinib has been investigated in clinical trials for patients who have progressed on earlier EGFR-targeted treatments. It penetrates the central nervous system effectively, making it a candidate for treating brain metastases in EGFR-mutant NSCLC. Although development was discontinued in later stages due to strategic decisions rather than safety or efficacy failures, it contributed valuable insights into the design of next-generation EGFR inhibitors.