Fig. 1

Structures of EGFR-TKIs used in this study. The first- and second-generation EGFR-TKIs both have anilino (blue square)-quinazoline (red square) structures. However, the second-generation TKIs also have an acrylamide group (orange square), which serves as a chemically reactive Michael acceptor electrophile that targets a cysteine nucleophile (Cys797), resulting in a covalent adduct. The third-generation EGFR-TKIs are pyrimidine (green square)-based compounds with an acrylamide group (orange square) for covalent binding to the EGFR