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Lenvatinib (E7080)

现货
Catalog No.
A2174
VEGFR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 750.00
现货
5mg
¥ 700.00
现货
25mg
¥ 3,000.00
现货
100mg
¥ 8,000.00
现货

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Background

Lenvatinib (E7080) is an inhibitor of multiple RTK with IC50 values of 22nM, 4nM, 5.2nM, 39nM and 35nM on VEGFR-1, VEGFR-2, VEGFR-3, PDGFRβ and RET, respectively [1].

Lenvatinib is presently under investigation both as monotherapy and in combination with cytotoxic agents for multiple types of solid tumor, including thyroid carcinoma and hepatocellular carcinoma (in Phase III trials), and melanoma, renal carcinoma, non-small cell lung carcinoma, glioblastoma multiforme, and ovarian and endometrial carcinoma (Phase I and II trials) [1].

When used as an inhibitor of RET kinase, Lenvatinib cause growth inhibition in TPC-1 cells and LC-2/ad cells. The GI50 values are 27nM and 48nM. It is also reported that Lenvatinib can inhibit RET (rearranged during transfection) gene fusion kinases, and inhibit oncogenic signaling of RET gene fusions. Lenvatinib has been demonstrated to exert antitumor activities in RET gene fusion-driven tumor models [2].

References:
[1] Neda Stjepanovic, Jaume Capdevila. Multikinase inhibitors in the treatment

of thyroid cancer: specific role of lenvatinib. Biologics: Targets and Therapy. 2014 (8): 129-139.

[2] Kiyoshi Okamoto, Kotaro Kodama, Kazuma Takase, Naoko Hata Sugi, Yuji Yamamoto, Masao Iwata, Akihiko Tsuruoka. Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models. Cancer Letters. 2013 July(340):97-103.

Chemical Properties

StorageStore at -20°C
M.Wt426.85
Cas No.417716-92-8
FormulaC21H19ClN4O4
Solubility≥21.35mg/mL in DMSO
Chemical Name4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxyquinoline-6-carboxamide
SDFDownload SDF
Canonical SMILESCOC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

HUVECs

制备方法

在DMSO中的溶解度大于21.4 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

0 ~ 10 μM;72小时

实验结果

在VEGF和VEGF-C刺激的HUVEC中,Lenvatinib显著抑制VEGF-R2和VEGF-R3,其IC50值分别为0.83 nM和0.36 nM。此外,E7080对VEGF诱导的HUVECs增殖的抑制活性 (IC50 = 2.7 nmol/L)显著高于对基础FGF诱导的HUVECs增殖 (IC50 = 410 nM) 以及PDGF诱导的L细胞增殖 (IC50 = 340 nM) 的抑制活性。

动物实验 [1]:

动物模型

携带MDA-MB-231细胞的裸小鼠

给药剂量

100 mg/kg;口服给药;每天1次,持续8周

实验结果

在携带MDA-MB-231细胞的裸小鼠中,E7080显著抑制肿瘤生长,其RTV值为0.81 ± 1.00。E7080也显著抑制MDA-MB-231细胞转移到局部淋巴结以及远端肺部。此外,E7080也减少MDA-MB-231异种移植瘤模型淋巴结转移性结节内的血管生成和淋巴管生成。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Matsui J, Funahashi Y, Uenaka T, Watanabe T, Tsuruoka A, Asada M. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res. 2008 Sep 1;14(17):5459-65.

生物活性

描述 Lenvatinib是多靶点RTK抑制剂,作用于VEGFR-1、VEGFR-2、VEGFR-3、PDGFRβ和RET,IC50值分别为22 nM、4 nM、5.2 nM、39 nM和35 nM。
靶点 VEGFR-1 VEGFR-2 VEGFR-3 PDGFRβ RET  
IC50 22 nM 4 nM 5.2 nM 39 nM 35 nM  

质量控制