| Identification | Back Directory | [Name]
PD04217903 | [CAS]
956905-27-4 | [Synonyms]
CS-527
CS-1921
PD04217903
PF-04217903cas
PD04217903 USP/EP/BP
PF-04217903;PF 04217903
2-[4-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol
1H-Pyrazole-1-ethanol, 4-[1-(6-quinolinylmethyl)-1H-1,2,3-triazolo[4,5-b]pyrazin-6-yl]-
2-{4-[1-(6-Quinolinylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-y l]-1H-pyrazol-1-yl}ethanol
2-[4-[1-(Quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]-1H-pyrazol-1-yl]ethanol
2-(4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyrazin-5-yl)-1H-pyrazol-1-yl)ethanol
PF 04217903
2-[4-[1-(Quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]-1H-pyrazol-1-yl]ethanol
2-[4-[1-(Quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]-1H-pyrazol-1-yl]ethanol PF 04217903 | [Molecular Formula]
C19H16N8O | [MDL Number]
MFCD12407410 | [MOL File]
956905-27-4.mol | [Molecular Weight]
372.39 |
| Chemical Properties | Back Directory | [Boiling point ]
718.1±60.0 °C(Predicted) | [density ]
1.53 | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in EtOH; insoluble in H2O; ≥18.6 mg/mL in DMSO | [form ]
solid | [pka]
14.31±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
4-[1-(6-Quinolinylmethyl)-1H-1,2,3-triazolo[4,5-b]pyrazin-6-yl]-1H-pyrazole-1-ethanol is a potential targets for protein kinase inhibitors on the regulation of autophagy. A potent and selective c-MET receptor tyrosine kinase. Potent c-MET inhibitor. | [Definition]
ChEBI: 2-[4-[3-(6-quinolinylmethyl)-5-triazolo[4,5-b]pyrazinyl]-1-pyrazolyl]ethanol is a member of quinolines. | [Biological Activity]
pf-04217903 is an atp-competitive small-molecule inhibitor of c-met kinase with ki value of 4.8 nm [1].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 [1].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 [1 and 2].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 [1]. | [in vivo]
PF-04217903 (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 (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 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 h y, li q, lee j h, et al. sensitivity of selected human tumor models to pf-04217903, a novel selective c-met kinase inhibitor. molecular cancer therapeutics, 2012, 11(4): 1036-1047.
[2] cui j j, mctigue m, nambu m, 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)-1 h-[1, 2, 3] triazolo [4, 5-b] pyrazin-6-yl)-1 h-pyrazol-1-yl) ethanol (pf-04217903) for the treatment of cancer. journal of medicinal chemistry, 2012, 55(18): 8091-8109. |
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| Company Name: |
ChemCell Biomedicine Co.,Ltd.
|
| Telephone: |
020-13556033878 2965585218 13556033878 |
| Website: |
https://www.chemicalbook.com/ShowSupplierProductsList15061/0_EN.htm |
| Company Name: |
NCE Biomedical Co.,Ltd.
|
| Telephone: |
4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15748/0_EN.htm |
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