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PF-04217903 methanesulfonate
Cat No.
CEI-1468
Description
PF-04217903 methanesulfonate is a selective ATP-competitive inhibitor of c-Met with IC50 value of 4.8 nM.
Product Overview
PF-04217903 is an ATP-competitive small-molecule inhibitor of c-Met kinase with Ki value of 4.8 nM. The c-Met kinase is a kind of receptor tyrosine kinases (RTK) and plays critical roles in embryonic development and wound healing. Activation of c-Met by the exclusive ligand hepatocyte growth factor (HGF) triggers a serious of biological responses that collectively give rise to the invasive growth. In cancers, abnormal activation of c-METs correlates with tumor growth, formation of new blood vessels and subsequently poor prognosis. PF-04217903 is a highly selective inhibitor of c-Met. It showed antitumor activity in tumor models where c-Met is activated by mechanisms including c-Met gene amplification, HGF/c-Met autocrine loop formation or c-Met overexpression. PF-04217903 showed more than 1000-fold greater selectivity against c-Met kinase over 150 other kinases. When evaluated in a panel of human tumor and endothelial cell lines such as GTL-16, H1993 and HT29 cells, PF-04217903 showed inhibition of c-Met with a mean IC50 value of 7.3 nM. PF-04217903 was also found to inhibit some mutant c-Met including R988C (IC50 value of 6.4 nM), V1092I (IC50 value of 16 nM), H1094R (IC50 value of 3.1 nM), M1250T (IC50 value of 24 nM) and T11010I (IC50 value of 6.7 nM). Besides that, PF-04217903 suppressed proliferation of c-Met-amplified GTL-16 and H1993cells with IC50 values of 12 and 30 nM, respectively. It induced apoptosis in GTL-16 cells. In mice bearing injected GTL-16 tumors, administration of PF-04217903 showed dose-dependent c-Met phosphorylation inhibition and antitumor efficacy. It inhibited the phosphorylation of c-Met with EC50 value of 10 nM and suppressed tumor growth with EC50 value of 13 nM. Moreover, PF-04217903 was found to affect the downstream signal transduction of c-Met such as AKT, STAT5 and Gab-1.
CAS No.
956906-93-7
Molecular Weight
468.49
Purity
0.98
Storage
Store at +4°C
Synonyms
PF04217903 mesylate
Targets
c-Met
IC50
4.8 nM
Molecular Formula
C20H20N8O4S
Chemical Name
methanesulfonic acid; 2-[4-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol
Solubility
Soluble in DMSO > 10 mM
Shipping Conditions
Evaluation sample solution: ship with blue ice. All other available size: ship with RT, or blue ice upon request
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