A13

A13 is a preclinical, reversible small molecule tyrosine kinase inhibitor (TKI) belonging to the 2-aminopyrimidine class. It was specifically designed to address the clinical challenge of drug resistance in non-small cell lung cancer (NSCLC) caused by the EGFR C797S mutation, particularly the triple mutation EGFR Del19/T790M/C797S. A13 exhibits significant anti-proliferative activity and high selectivity against resistant cell lines, such as the KC-0116 line. Mechanistically, it functions as an ATP-competitive inhibitor that binds to the orthosteric pocket of the EGFR kinase domain, forming essential hydrogen bonds with the Met793 residue in the hinge region. This binding inhibits EGFR phosphorylation, arrests the cell cycle, and induces apoptosis in resistant cancer cells.