WZ4002

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

WZ4002 是一种新型突变选择性 EGFR 抑制剂，针对 EGFR(L858R)/(T790M)，IC50 为 2 nM/8 nM。

WZ4002 is a novel, mutant-selective EGFR inhibitor for EGFR(L858R)/(T790M) with IC50 of 2 nM/8 nM; does not inhibit ERBB2 phosphorylation (T798I).(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.(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.

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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.

WZ4002 | WZ-4002 | WZ 4002

Angiogenesis

EGFR

EGFR (L858R)| EGFR (L858R/T790M)

Cancer

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1213269-23-8

494.18

C25H27ClN6O3

>98% (HPLC)

DMSO:13 mg/mL (26.3 mM);Ethanol:<1 mg/mL (<1 mM);Water：<1 mg/mL (<1 mM)

C=CC(NC1=CC=CC(OC2=NC(NC3=CC=C(N4CCN(C)CC4)C=C3OC)=NC=C2Cl)=C1)=O

N-(3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)acrylamide

(-20℃)

With Ice Pack

≥ 2 years