JBJ-09-063 hydrochloride is an EGFR inhibitor selective for mutants, demonstrating IC50 values of 0.147 nM, 0.063 nM, 0.083 nM, and 0.396 nM against EGFR L858R, EGFR L858R/T790M, EGFR L858R/T790M/C797S, and EGFR L747S, respectively. It effectively inhibits EGFR, Akt, and ERK1/2 phosphorylation, showing efficacy in both EGFR tyrosine kinase inhibitor (TKI)-sensitive and -resistant models. This compound holds potential for research on EGFR-mutant lung cancer.