WZ8040

WZ8040 is an inhibitor of mutant EGF receptors (EGFRs) with IC₅₀ values ranging from 2 to 306 nM in Ba/F3 cells. It is selective for EGFR mutants, including the EGFR^{Del E746_A750} and EGFR^L858R mutations conferring gefitinib sensitivity and the EGFR^{Del E746_A750/T790M} mutation conferring gefitinib resistance (IC₅₀s = 2, 6, and 6 nM in Ba/F3 cells), over wild-type EGFR (IC₅₀ = 1,820 nM in HN11 cells) but also inhibits ERBB2^{Ins G776V,C} and wild-type ERBB2 (IC₅₀s = 20 and 32 nM, respectively, in Ba/F3 cells). WZ8040 inhibits proliferation of PC-9 cells harboring the EGFR^{Del E746_A750} mutation and gefitinib-resistant PC-9 GR cells harboring the EGFR^T790M resistant allele (EC₅₀s = 6 and 8 nM, respectively).

WZ8040 is an irreversiblely EGFR T790M inhibitor (IC50<10nM).