WZ4002 is a mutant selective EGFR inhibitor with IC50s of 2, 8, 3 and 2 nM for EGFR, EGFR, EGFR and EGFR, respectively.
性状
Solid
IC50 & Target[1][2]
EGFR
2 nM (IC50, Cell Assay)
EGFR
8 nM (IC50, Cell Assay)
EGFR
3 nM (IC50, Cell Assay)
EGFR
2 nM (IC50, Cell Assay)
体外研究(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 EGFR mutant alleles. WZ4002 inhibits EGFR kinase activity of recombinant L858R/T790M protein more potently than of WT EGFR.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究(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.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.