ASP8273 is an irreversible TKI small molecule inhibitor that inhibits the kinase activity of EGFR mutants including T97M with limited activity against wild-type EGFR. In in vitro enzymatic activity and cellular assays, ASP8273 covalently bound to an EGFR mutant (L858R/T790M) through cysteine residues and long-term inhibited EGFR phosphorylation for 24 hours. In NSCLC cell lines with the above-mentioned EGFR mutations, ASP8273 has IC50 values in the range of 8-33 nM for EGFR mutants, more potent than WT EGFR (IC50 for WT EGFR is 230 nM).
