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Golvatinib

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Chemical Structure| 928037-13-2 同义名 : E-7050
CAS号 : 928037-13-2
货号 : A133170
分子式 : C33H37F2N7O4
纯度 : 99%+
分子量 : 633.688
MDL号 : MFCD22124462
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(78.9 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

30% propylene glycol+5% Tween 80+65% water 30 mg/mL suspension

生物活性
靶点

  • VEGFR2

    VEGFR2, IC50:16 nM
描述 The protein product of the MET proto-oncogene, c-Met, a receptor tyrosine kinase (RTK), is a prototype for the c-Met RTK subfamily and is activated by the ligand hepatocyte growth factor (HGF; scatter factor). Activation of the HGF/c‐Met pathway causes tumor progression, invasion, and metastasis[3]. Moreover, the c-Met signaling pathway engages with other pathways, including that of the EGFR/human EGFR/MAPK/ERK pathway and can also promote angiogenesis through interaction with the VEGF and VEGF receptor (VEGFR) pathway. In addition, c-Met signaling can downregulate the antiangiogenic thrombospondin-1 and upregulate VEGF and upregulation of HGF and c-Met occurs after VEGF inhibition. Golvatinib (E7050, Eisai) is a highly potent, small-molecule, ATP-competitive inhibitor of c-Met and multiple members of the Eph receptor family, as well as c-Kit and Ron, with an IC50 for c-Met of 0.001 μM[4]. E7050 inhibits both c-Met and vascular endothelial growth factor receptor (VEGFR)-2 and inhibits phosphorylation of both c-Met and VEGFR-2. E7050 also potently represses the growth of both c-Met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. In a vitro study, MKN45 (gastric), SNU-5 (gastric), Hs746T (gastric), EBC-1 (lung), MKN74 (gastric), SNU-1 (gastric), A549 (lung) cell lines were treated with c-Met nonselective inhibitor E7050 at a dose ranging in 50-200 mg/kg to induce tumor regression and disappearance, indicating that E7050 is an efficient inhibitor of c-Met by inhibited phosphorylation of c-Met in tumors. In a vivo study, After different tumor cells were implanted subcutaneously (s.c.) into the mice respectively, E7050 was administered orally once a day at dose ranging from 25 mg/kg to 200 mg/kg for 8 to 15 days, suggesting that E7050 showed inhibition of the phosphorylation of c-Met in tumors, and strong inhibition of tumor growth and tumor angiogenesis. In a peritoneal dissemination model, MKN45 cells were inoculated intraperitoneally into nude mice and treated with E7050 at dose ranging from 25 mg/kg to 100 mg/kg for 6 days. E7050 showed an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. The results indicate that E7050 is a potent inhibitor of c-Met and VEGFR-2 and has therapeutic potential for the treatment of cancer[3].
作用机制 Golvatinib binds to the MET enzyme with a 2-aminopyridine hinge binder.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.58mL

0.32mL

0.16mL

7.89mL

1.58mL

0.79mL

15.78mL

3.16mL

1.58mL
参考文献

[1]Wang W, Li Q, et al. 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.

[2]Nakagawa T, Tohyama O, et al. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5.

[3]Nakagawa T, Tohyama O, Yamaguchi A, Matsushima T, Takahashi K, Funasaka S, Shirotori S, Asada M, Obaishi H. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5. doi: 10.1111/j.1349-7006.2009.01343.x. Epub 2009 Sep 2. PMID: 19832844.

[4]Molife LR, Dean EJ, Blanco-Codesido M, Krebs MG, Brunetto AT, Greystoke AP, Daniele G, Lee L, Kuznetsov G, Myint KT, Wood K, de Las Heras B, Ranson MR. A phase I, dose-escalation study of the multitargeted receptor tyrosine kinase inhibitor, golvatinib, in patients with advanced solid tumors. Clin Cancer Res. 2014 Dec 15;20(24):6284-94. doi: 10.1158/1078-0432.CCR-14-0409. Epub 2014 Oct 2. PMID: 25278451.