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 EGFRDel E746_A750 and EGFRL858R mutations conferring gefitinib sensitivity and the EGFRDel 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 ERBB2Ins 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 EGFRDel E746_A750 mutation and gefitinib-resistant PC-9 GR cells harboring the EGFRT790M resistant allele (EC50s = 6 and 8 nM, respectively).
