ZW-49 is a potent, selective and covalent inhibitor of all subgroups of EGFR mutations with IC50 of 1.5 nM (EGFR L858R/T790M), potently inhibits all subgroups of EGFR mutations with selectivity over wild-type EGFR and other target families.
ZW-49 shows potent anti-proliferative activity against NCI-H1975 (EGFR L858R/T790M) and HCC827 (EGFR Ex19del) with IC50 of 12 nM and 4 nM respectively, only shows moderate anti-proliferative activity for A431 (WT EGFR overexpression) cells (IC50=103 nM).
ZW-49 exhibits significant enzymatic inhibition against all tested EGFR PACC, Ex20ins, and HER2 mutants with IC50 values ranging from 0.03 to 0.41 nM.
ZW-49 shows potent cellular activity against Ba/F3 cells expressing EGFR Ex20ins (ASV, NPH, SVD, and H) mutants, and mutations G719A (PACC) and L861Q (classical-like) bearing Ba/F3 cells (IC50=0.58 and 0.98 nM).
ZW-49 blocks the G0/G1 cell cycle, triggered apoptosis, and selectively inhibits the growth of EGFR L858R/T790M mutant H1975 cells by modulating the EGFR signaling pathway.
W-49 (5 and 10 mg/kg) inhibited tumor growth in the NCI-H1975 model, ZW-49 at 25 mg/kg exhibited excellent antitumor activity with a TGI of 120.27%.