Foretinib

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本试剂(Foretinib)
仅供科研实验使用,不得用于其他用途！

简介：
货 号：F-4185
名 称：Foretinib
别 名：Foretinib Free Base
C A S ：849217-64-7
分子量：632.65
分子式：C34H34F2N4O6
纯 度：HPLC/TLC:>99%
说 明：Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 150 mg/mL; soluble in ethanol at 5 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-10 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A.
文 献：Foretinib inhibited receptor tyrosine kinases (RTKs) in vitro with IC50 values of 0.4 nM for Met and 3 nM for Ron. It inhibited cellular Met with IC50 values of 23 nM in PC-3 prostate cells and 21 nM in murine B16F10 melanoma cells. It also reduced tumor cell migration, invasion, and endothelial tubule formation. Foretinib had cytotoxic activities against a broad panel of cell lines. It also blocked lung metastasis after the implantation of B16F10 solid tumors in mice. Qian, F., et al. "Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases." Cancer Res. 69: 8009-8016 (2009). MET-amplified tumor lines with HER1 or HER2 amplification are more sensitive to the combination of foretinib with lapatinib or erlotinib. MET-overexpressing tumor cell lines with HER1 or HER2 amplification are less sensitive to lapatinib or erlotinib in the presence of HGF. Foretinib can reverse the effect of HGF on lapatinib or erlotinib sensitivity in these cells. Liu, L., et al. "Synergistic effects of foretinib with HER-targeted agents in MET and HER1- or HER2-coactivated tumor cells." Mol. Cancer Ther. 10: 518-530 (2011). Foretinib inhibits tumorigenesis and blocks invasive tumor growth in different models of ovarian cancer by affecting several critical tumor functions including inducing anoikis (anchorage-dependent programmed cell death) and inhibiting (1) c-Met activation and downstream signaling, (2) ovarian cancer cell adhesion, (3) migration and invasion, and (4) proliferation. Zillhardt, M., et al. "Foretinib (GSK1363089), an orally available multikinase inhibitor of c-Met and VEGFR-2, blocks proliferation, induces anoikis, and impairs ovarian cancer metastasis." Clin. Cancer Res. 17: 4042-4051 (2011) Foretinib potently block multiple RTKs, including VEGF receptor and the receptor of HGF c-Met. Inhibition of c-Met and functionally related kinases intensifies the effects of VEGF receptor blockade, which leads to regression of tumor vasculature. You, W.K., et al. "VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer." Cancer Res. 71: 4758-4768 (2011). Foretinib caused mitotic catastrophe in chronic myelogenous leukemia cells and other cell lines by JNK-dependent inhibition of Plk1 expression and induced apoptosis via a caspase 2-mediated mechanism. Dufies, M., et al. "Mechanism of action of the multikinase inhibitor Foretinib." Cell Cycle 10: 4138-4148 (2011). Foretinib had cytotoxic effects against gastric cancer cells harboring MET and FGFR2 amplification. It exerted its cytotoxic effects by blocking inter-RTK signaling networks with MET or FGFR2 at their center. Kataoka, Y., et al. "Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks." Invest. New Drugs 30: 1352-1360 (2012). Foretinib was shown to have significant antitumor activities in patient-derived hepatocellular carcinoma xenograft models. Huynh, H., et al. "Foretinib demonstrates anti-tumor activity and improves overall survival in preclinical models of hepatocellular carcinoma." Angiogenesis 15: 59-70 (2012).