Small Molecular Raw API Powder Wz4002 (CAS# 1213269-23-8)

Description  

WZ4002 is a novel, mutant-selective inhibitor of EGFR for EGFR(L858R)/(T790M) with IC50 of 2 nM/8 nM. 

WZ4002 inhibits other EGFR genotypes E746_A750 and E746_A750/T790M with IC50 of 2 and 6 nM. Besides, WZ4002 suppresses widetype ERBB2 with an IC50 of 32 nM. WZ4002 inhibits EGFR, AKT and ERK1/2 phosphorylation in NSCLC cell lines and WZ4002 prevents of EGFR phosphorylation in NIH-3T3 cells expressing different EGFR T790M mutant alleles. For WZ4002, kinases that exhibited greater than 95% inhibition relative to the DMSO control at 10 μM are selected for measurement of their dissociation constants. WZ4002, which possesses an ortho-methoxy group at the C2-aniline substituent, is more selective for EGFR compared to WZ3146. WZ4002 is 100-fold less effective at inhibiting phosphorylation of WT EGFR compared to the quinazoline inhibitors. Similarly, WZ4002 prevents EGFR kinase activity of recombinant L858R/T790M protein more potently than of WT EGFR, while the opposite is observed with HKI-272 . In addition, the phosphorylated EGFR of Src TKI-resistant H1975 cells, as well as HCC827 cells, is completely suppressed by the third generation EGFR TKI, WZ4002.

 

Application

Treatment with WZ4002 completely inhibited the growth of PC-9/Vec tumors, whereas treatment with E7050 did not (Fig. A). Treatment with either agent a lone slightly suppressed the growth of PC- 9/HGF#5 t umor s ( Fig. B). Importantly, the combination of WZ4002 and E7050 reduced the size of PC-9/HGF#5 tumors(Fig.B).These results suggest that HGF can induce resistance to WZ4002 in vivo and that this resistance can be overcome by E7050. In the second model, the growth of tumors induced by H1975 cells, which carry a T790M second mutation, was inhibited by WZ4002 (Fig. C), In the third model, in which resistance was induced by Met amplification, monotherapy with either WZ4002 or E7050 partially inhibited the growth of HCC827ER tumors(Fig. D)

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Description  

WZ4002 is a novel, mutant-selective inhibitor of EGFR for EGFR(L858R)/(T790M) with IC50 of 2 nM/8 nM. 

WZ4002 inhibits other EGFR genotypes E746_A750 and E746_A750/T790M with IC50 of 2 and 6 nM. Besides, WZ4002 suppresses widetype ERBB2 with an IC50 of 32 nM. WZ4002 inhibits EGFR, AKT and ERK1/2 phosphorylation in NSCLC cell lines and WZ4002 prevents of EGFR phosphorylation in NIH-3T3 cells expressing different EGFR T790M mutant alleles. For WZ4002, kinases that exhibited greater than 95% inhibition relative to the DMSO control at 10 μM are selected for measurement of their dissociation constants. WZ4002, which possesses an ortho-methoxy group at the C2-aniline substituent, is more selective for EGFR compared to WZ3146. WZ4002 is 100-fold less effective at inhibiting phosphorylation of WT EGFR compared to the quinazoline inhibitors. Similarly, WZ4002 prevents EGFR kinase activity of recombinant L858R/T790M protein more potently than of WT EGFR, while the opposite is observed with HKI-272 . In addition, the phosphorylated EGFR of Src TKI-resistant H1975 cells, as well as HCC827 cells, is completely suppressed by the third generation EGFR TKI, WZ4002.

 

Application

Treatment with WZ4002 completely inhibited the growth of PC-9/Vec tumors, whereas treatment with E7050 did not (Fig. A). Treatment with either agent a lone slightly suppressed the growth of PC- 9/HGF#5 t umor s ( Fig. B). Importantly, the combination of WZ4002 and E7050 reduced the size of PC-9/HGF#5 tumors(Fig.B).These results suggest that HGF can induce resistance to WZ4002 in vivo and that this resistance can be overcome by E7050. In the second model, the growth of tumors induced by H1975 cells, which carry a T790M second mutation, was inhibited by WZ4002 (Fig. C), In the third model, in which resistance was induced by Met amplification, monotherapy with either WZ4002 or E7050 partially inhibited the growth of HCC827ER tumors(Fig. D)

Report:
FEATURED PRODUCT: