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• 产品描述： Golvatinib is an orally bioavailable dual kinase inhibitor of c-Met (hepatocyte growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) tyrosine kinases with potential antineoplastic activity. c-Met/VEGFR kinase inhibitor E7050 binds to and inhibits the activities of both c-Met and VEGFR-2, which may inhibit tumor cell growth and survival of tumor cells that overexpress these receptor tyrosine kinases. c-Met and VEGFR-2 are upregulated in a variety of tumor cell types and play important roles in tumor cell growth, migration and angiogenesis.

• 靶点： c-Met/HGFR;VEGFR;VEGFR; c-Met/HGFR

• 体外研究：
  Golvatinib (E-7050) potently inhibits phosphorylation of both c-Met and VEGFR-2. Golvatinib also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF.
  Golvatinib strongly inhibits the growth of MKN45, EBC-1, Hs746T, and SNU-5 tumor cells with IC50 values of 37, 6.2, 23, and 24 nM, respectively. The growth of A549, SNU-1 and 0MKN74 tumor cells is inhibited by Golvatinib with much higher IC50 values.
  Golvatinib circumvents resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro.
  Golvatinib also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF.

• 体内研究：
  In vivo studies using E7050 shows inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models. Treatment of some tumor lines containing c-met amplifications with high doses of E7050 (50–200 mg/kg) induces tumor regression and disappearance. In a peritoneal dissemination model, E7050 shows an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. [1] In another xenograft model research, tumors produced by HGF-transfected Ma-1 (Ma-1/HGF) cells are more angiogenic than vector control tumors and shows resistance to ZD1839. E7050 alone inhibits angiogenesis and retards growth of Ma-1/HGF tumors. E7050 combined with ZD1839 induces marked regression of tumor growth.

• 细胞实验： Cells (1–3 × 103 cells/100 μL/well) are seeded on 96-well culture plates with various concentrations of E7050 and cultured for 3 days. Then, 10 μL of WST-8 reagent is added to each well, and absorbance is measured at 450 nm compared with a reference measurement at 660 nm using a MTP-500 microplate reader. HUVEC (2 × 103 cells/well) are cultured for 3 days in medium containing HGF (30 ng/mL), VEGF (20 ng/mL), or basic fibroblast growth factor (bFGF) (20 ng/mL) together with serially diluted E7050.(Only for Reference)

• 动物实验： Mice: Nude mice bearing MKN45, Hs746T, SNU-5, or EBC-1 tumors are administered Golvatinib (25, 50, 100, 200 mg/kg) or vehicle only as a control, once a day. Tumor volume is measured using calipers on the indicated days (0-15 days)

• 参考文献：
  1: Nakagawa T, Takeuchi S, Yamada T, Nanjo S, Ishikawa D, Sano T, Kita K, Nakamura T, Matsumoto K, Suda K, Mitsudomi T, Sekido Y, Uenaka T, Yano S. Combined Therapy with Mutant-Selective EGFR Inhibitor and Met Kinase Inhibitor for Overcoming Erlotinib Resistance in EGFR-Mutant Lung Cancer. Mol Cancer Ther. 2012 Oct;11(10):2149-57. doi: 10.1158/1535-7163.MCT-12-0195. Epub 2012 Jul 25. PubMed PMID: 22844075.
  2: Takeuchi S, Wang W, Li Q, Yamada T, Kita K, Donev IS, Nakamura T, Matsumoto K, Shimizu E, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Dual inhibition of Met kinase and angiogenesis to overcome HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer. Am J Pathol. 2012 Sep;181(3):1034-43. doi: 10.1016/j.ajpath.2012.05.023. Epub 2012 Jul 9. PubMed PMID: 22789825.
  3: Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res. 2012 Mar 15;18(6):1663-71. Epub 2012 Feb 8. PubMed PMID: 22317763.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	1.578 ml	7.89 ml	15.781 ml
  5 mM	0.316 ml	1.578 ml	3.156 ml
  10 mM	0.158 ml	0.789 ml	1.578 ml
  50 mM	0.032 ml	0.158 ml	0.316 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *