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).

EGFR T790M

[1] zhou w1, ercan d, chen l, yun ch, li d, capelletti m, cortot ab, chirieac l, iacob re, padera r, engen jr, wong kk, eck mj, gray ns, jänne pa. novel mutant-selective egfr kinase inhibitors against egfr t790m. nature. 2009 dec 24;462(7276):1070-4. doi: 10.1038/nature08622.