WZ8040

N-(3-(5-chloro-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-ylthio)phenyl)acrylamide

WZ8040 is a novel mutant-selective irreversible EGFRT790M inhibitor.

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 uM, 738 nM, 915 nM, 744 nM, and 1.82 uM, respectively. WZ8040 is not toxic up to 10 uM 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.

WZ8040 Chemical Structure

, , Dr. Yong-Weon Yi from Georgetown University Medical Center, WZ8040purchased from Selleck, For MTT assays, cells (2, 000 ca. 5, 000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of WZ8040 by adding 20 l of 5 mg/ml 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) solution per 100 l of growth medium. After incubating for 3-4 h at 37C, the media were removed and 150 l/well of MTT solvent (either absolute DMSO or isopropanol containing 4 M HCl and 0.1% Nonidet-40) was added to dissolve the formazan.

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO