1159490-83-1
Chemical Structure
PF-04217903 phosphate
- CAS No.: 1159490-83-1
- Formula:C19H19N8O5P
- Molecular Weight:470.38
InChIKey: TWWONGIWZWOGQN-UHFFFAOYSA-N
SMILES: O=P(O)(O)O.OCCN1N=CC(C2=NC3=C(N=C2)N=NN3CC4=CC5=CC=CN=C5C=C4)=C1
Biological Activity: PF-04217903 phosphate is an orally active, highly selective ATP-competitive c-Met kinase inhibitor with a Ki value of 4.8 nM and a Kd value of 4.5 nM. PF-04217903 phosphate blocks c-Met and HGF signaling pathways, inhibits MET phosphorylation, and blocks downstream MAPK, PI3K/AKT and PLCγ1 pathways. PF-04217903 phosphate suppresses tumor proliferation, survival, migration, invasion, angiogenesis and metastasis, induces apoptosis, and enhances efferocytosis, Annexin A1 expression and resolution of inflammation. PF-04217903 phosphate retains activity against several c-Met mutants (M1131T, V1220I, H1094R). PF-04217903 phosphate increases the incidence of subarachnoid hemorrhage and reduces survival rate without altering aneurysm formation, and also prevents lymph node metastasis induced by VEGF inhibition. PF-04217903 phosphate is applicable to research related to tumors (pancreas, stomach, lung, brain, colon, breast, kidney, melanoma, etc.), intracranial aneurysms and inflammatory diseases (gouty arthritis, neutrophilic pleuritis)[1][2][3][4][5][6][7][8][9].
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PF-04217903 phosphate | PF-04217903 phosphate is an orally active, highly selective ATP-competitive c-Met kinase inhibitor with a Ki value of 4.8 nM and a Kd value of 4.5 nM. PF-04217903 phosphate blocks c-Met and HGF signaling pathways, inhibits MET phosphorylation, and blocks downstream MAPK, PI3K/AKT and PLCγ1 pathways. PF-04217903 phosphate suppresses tumor proliferation, survival, migration, invasion, angiogenesis and metastasis, induces apoptosis, and enhances efferocytosis, Annexin A1 expression and resolution of inflammation. PF-04217903 phosphate retains activity against several c-Met mutants (M1131T, V1220I, H1094R). PF-04217903 phosphate increases the incidence of subarachnoid hemorrhage and reduces survival rate without altering aneurysm formation, and also prevents lymph node metastasis induced by VEGF inhibition. PF-04217903 phosphate is applicable to research related to tumors (pancreas, stomach, lung, brain, colon, breast, kidney, melanoma, etc.), intracranial aneurysms and inflammatory diseases (gouty arthritis, neutrophilic pleuritis). | |||||||||||||||||||||
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- [1]. Sennino B, et al. Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer discovery. 2012 Mar;2(3):270-87. [Content Brief]
- [2]. Sennino B, et al. Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice. Cancer research. 2013 Jun 15;73(12):3692-703. [Content Brief]
- [3]. Peña-Silva RA, et al. Novel role for endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms. Hypertension. 2015 Mar;65(3):587-93. [Content Brief]
- [4]. Knauf JA, et al. Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers. The Journal of clinical investigation. 2018 Aug 31;128(9):4086-4097. [Content Brief]
- [5]. Felix FB, et al. Blocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis. Pharmacological research. 2023 Feb;188:106640. [Content Brief]
- [6]. Zou HY, et al. Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Molecular cancer therapeutics. 2012 Apr;11(4):1036-47. [Content Brief]
- [7]. Wu Y, et al. Peptide-Functionalized Nanoinhibitor Restrains Brain Tumor Growth by Abrogating Mesenchymal-Epithelial Transition Factor (MET) Signaling. Nano letters. 2018 Sep 12;18(9):5488-5498. [Content Brief]
- [8]. Lee NV, et al. A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells through [corrected] MAPK activation. PloS one. 2012;7(6):e39653. [Content Brief]
- [9]. 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. [Content Brief]
Keywords
