| 產(chǎn)品描述： | PF-04217903 mesylate is a potent ATP-competitive c-Met kinase inhibitor with Ki of 4.8 nM for human c-Met. PF-04217903 mesylate shows more than 1,000-fold selectivity relative to 208 kinases. Antiangiogenic properties |
| 靶點： |
Ki: 4.8 nM (human c-Met);c-Met/HGFR |
| 體外研究： |
PF-04217903 mesylate (0.1-10000 nM; 48-72 hours) inhibits proliferation of c-Met–amplified human GTL-16 gastric carcinoma and H1993 NSCLC cells with IC50 values of 12 and 30 nM, respectively[1].PF-04217903 mesylate induces apoptosis of GTL-16 cells (IC50=31 nM) . PF-04217903 mesylate also inhibits HGF-mediated cell migration and Matrigel invasion in several c-Met–overexpressing tumor cell lines such as human NCI-H441 lung carcinoma and HT29 colon carcinoma with IC50 values comparable with those for inhibition of c-Met phosphorylation in these cell lines (IC50= 7-12.5 nM). PF-04217903 mesylate displays similar potency to inhibit the activity of c-Met-H1094R, c-Met-R988C, and c-Met-T1010I with IC50 of 3.1 nM, 6.4 nM, and 6.7 nM, respectively, but has no inhibitory activity against c-Met-Y1230C with IC50 of >10 μM. Cell Proliferation Assay Cell Line: GTL-16, H1993 cells Concentration: 0.1, 1, 10, 100, 1000, 10000 nM Incubation Time: 48-72 hours Result: Inhibited proliferation of c-Met–amplified human GTL-16 gastric carcinoma and H1993 NSCLC cells with IC50 values of 12 and 30 nM, respectively. Apoptosis Analysis Cell Line: GTL-16 cells Concentration: 1.5-3333 nM Incubation Time: 48 hours Result: Induced apoptosis of GTL-16 cells (IC50=31 nM). |
| 體內(nèi)研究： |
PF-04217903 mesylate (1-30 mg/kg; p.o.; daily for 16 days) shows dose-dependent tumor growth inhibition, which correlated with the inhibition in c-Met phosphorylation in these tumors . PF-04217903 mesylate (5-50 mg/kg, p.o.; once daily for 3 days) dose dependently inhibits c-Met, Gab-1, Erk1/2, and AKT phosphorylation and induced apoptosis (cleaved caspase-3) in U87MG xenograft tumors at all dose levels. PF-04217903 mesylate shows a significant dose-dependent reduction of human IL-8 levels in both the U87MG and GTL-16 models and decreases human VEGFA levels in the GTL-16 model. PF-04217903 mesylate strongly induces phospho-PDGFRβ levels in U87MG xenograft tumors. Animal Model: Female nu/nu mice GTL-16 xenograft model Dosage: 1, 3, 10, 30 mg/kg Administration: Oral; daily for 16 days Result: Showed dose-dependent tumor growth inhibition, and was correlated with the inhibition in c-Met phosphorylation in these tumors. |
| 參考文獻： |
1. Timofeevski SL, et al. Enzymatic characterization of c-Met receptor tyrosine kinase oncogenic mutants and kinetic studies with aminopyridine and triazolopyrazine inhibitors. Biochemistry, 2009, 48(23), 5339-5349. 2. Shojaei F, et al. HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. Cancer Res, 2010, 70(24), 10090-10100. 3. Krumbach R, et al. Primary resistance to cetuximab in a panel of patient-derived tumour xenograft models: activation of MET as one mechanism for drug resistance. Eur J Cancer, 2011, 47(8), 1231-1243. |
| 溶解性： |
Soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.135 ml |
10.673 ml |
21.345 ml |
| 5 mM |
0.427 ml |
2.135 ml |
4.269 ml |
| 10 mM |
0.213 ml |
1.067 ml |
2.135 ml |
| 50 mM |
0.043 ml |
0.213 ml |
0.427 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權威性，僅供客戶參考交流研究之用。 |
上海工商
危險品化學品經(jīng)營許可證（不帶存儲）
營業(yè)執(zhí)照(三證合一)
北京