Biological Activity
WZ4002 is a mutant selective EGFR inhibitor with IC50s of 2, 8, 3 and 2 nM for EGFRL858R, EGFRL858R/T790M, EGFRE746_A750 and EGFRE746_A750/T790M, respectively.
In Vitro
WZ4002 increases cellular potency correlated with inhibition of EGFR, AKT and ERK1/2 phosphorylation in NSCLC cell lines and EGFR phosphorylation in NIH-3T3 cells expressing different EGFRT790M mutant alleles. WZ4002 inhibits EGFR kinase activity of recombinant L858R/T790M protein more potently than of WT EGFR[1].
In Vivo
In a pharmacodynamic study WZ4002 effectively inhibits EGFR, AKT and ERK1/2 phosphorylation which is associated with a significant increase in TUNEL positive and a significant decrease in Ki67 positive cells compared to vehicle alone treated mice. In a 2 week efficacy study, WZ4002 treatment results in significant tumor regressions compared to vehicle alone in both T790M containing murine models. Histological evaluation of the lungs following treatment confirms significant resolution of the tumor nodules with only few small residual nodules and nodule remnants that has evidence of treatment effect with decreased cellularity and increased fibrosis consistent with remodeling/scarring[1].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
