WZ8040 is a novel mutant-selective irreversible EGFRT790M inhibitor, does not inhibit ERBB2 phosphorylation (T798I).

Calu3 (ErbB2 amp):915 nM, H3255 cells (EGFR L858R):66 nM, H1975 cells (EGFR L858R/T790M):9 nM, H1781 cells (ErbB2 Ins G776V, C):744 nM, EGFR/ERBB2 (wildtype):1.82 μM (in HN11 cells), HCC827 GR cells (EGFR E746_A750/MET amp):>3.3 μM, HCC827 cells (EGFR Del E746_A750):1 nM, PC9 cells (EGFR Del E746_A750):6 nM, PC9 GR cells (EGFR Del E746_A750/T790M):8 nM, H1819 cells (ErbB2 amp):738 nM

WZ8040 is 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors such as CL-387785 and HKI-272. WZ8040 treatment potently inhibits the growth of HCC827 (EGFR Del E746_A750), PC9 (EGFR Del E746_A750), H3255 (EGFR L858R), H1975 (EGFR L858R/T790M), and PC9 GR (EGFR Del E746_A750/T790M) with IC50 of 1 nM, 6 nM, 66 nM, 9 nM, and 8 nM, respectively. WZ8040 weakly inhibits the growth of HCC827 GR (EGFR E746_A750/MET amp), H1819 (ERBB2 amp), Calu-3 (ERBB2 amp), H1781 (ERBB2 Ins G776V, C), and HN11 (EGFR & ERBB2 WT) with IC50 of >3.3 μM, 738 nM, 915 nM, 744 nM, and 1.82 μM, respectively. WZ8040 is not toxic up to 10 μM against A549 (KRAS mutant) or H3122 (EML4-ALK) cells. [1]

Cells are exposed to increasing concentrations of WZ8040 for 72 hours. Growth is assessed using the MTS survival assay.(Only for Reference)