| Identification | Back Directory | [Name]
PF-04217903 | [CAS]
1159490-85-3 | [Synonyms]
PF-04217903
aka PF-04217903
PF-04217903 phenolsulfonate
PF04217903 4-hydroxybenzenesulfonate
4-[1-(6-Quinolinylmethyl)-1H-1,2,3-triazolo[4,5-b]pyrazin-6-yl]-1H-pyrazole-1-ethanol 4-hydroxybenzenesulfonate | [Molecular Formula]
C25H22N8O5S | [MOL File]
1159490-85-3.mol | [Molecular Weight]
546.558 |
| Hazard Information | Back Directory | [Uses]
PF-04217903 phenolsulfonate is a potent ATP-competitive c-Met kinase inhibitor with Ki of 4.8 nM for human c-Met. PF-04217903 phenolsulfonate shows more than 1,000-fold selectivity relative to 208 kinases. Antiangiogenic properties[1][2]. | [Definition]
ChEBI: 2-[4-[3-(6-quinolinylmethyl)-5-triazolo[4,5-b]pyrazinyl]-1-pyrazolyl]ethanol is a member of quinolines. | [in vivo]
PF-04217903 phenolsulfonate (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[1].
PF-04217903 phenolsulfonate (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 phenolsulfonate 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 phenolsulfonate strongly induces phospho-PDGFRβ levels in U87MG xenograft tumors[1]. | Animal Model: | Female nu/nu mice (GTL-16 xenograft model)[1] | | 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.
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| [References]
[1] Zou HY, et al. Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther. 2012 Apr;11(4):1036-47. DOI:10.1158/1535-7163.MCT-11-0839
[2] Cui JJ, et al. Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor (c-MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (PF-04217903) for the treatment of cancer. J Med Chem. 2012 Sep 27;55(18):8091-109. DOI:10.1021/jm300967g
[3] Timofeevski SL, et al. Enzymatic characterization of c-Met receptor tyrosine kinase oncogenic mutants and kinetic studies with aminopyridine and triazolopyrazine inhibitors. Biochemistry. 2009 Jun 16;48(23):5339-49. DOI:10.1021/bi900438w |
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