乐伐替尼甲磺酸盐

乐伐替尼甲磺酸盐用途

Lenvatinib mesylate (E7080 mesylate),一种口服,多靶点酪氨酸激酶抑制剂,抑制血管内皮生长因子受体 (VEGFR1-3),成纤维细胞生长因子受体 (FGFR1-4),血小板衍生生长因子受体 (PDGFR),干细胞因子受体 (KIT),转染期间重排 (RET),显示有效抗癌的活性。

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乐伐替尼甲磺酸盐名称

[ CAS 号 ]:
857890-39-2

[ 中文名 ]:
乐伐替尼甲磺酸盐

[ 英文名 ]:
Lenvatinib Mesylate

[中文别名 ]:

[英文别名 ]:

Lenvatinib mesilate
lenvatinib mesylate
Lenvatinib mesylate [USAN]
Lenvatinib mesilate (JAN)
lenvatinib methanesulfonate
UNII-3J78384F61

乐伐替尼甲磺酸盐生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 癌症

信号通路 >> 蛋白酪氨酸激酶 >> PDGFR

信号通路 >> 蛋白酪氨酸激酶 >> FGFR

信号通路 >> 蛋白酪氨酸激酶 >> VEGFR

信号通路 >> 蛋白酪氨酸激酶 >> c-Kit

[ 靶点 ]

VEGFR1:22 nM (IC50)

VEGFR2:4 nM (IC50)

VEGFR3:5.2 nM (IC50)

FGFR1:46 nM (IC50)

FGFR2

FGFR3

FGFR4

PDGFRα:51 nM (IC50)

PDGFRβ:39 nM (IC50)

c-Kit:100 nM (IC50)

RET

[体外研究]

甲磺酸乐伐替尼(E7080甲磺酸酯)对VEGFR2(KDR),VEGFR3(Flt-4)和VEGFR1/Flt-1的IC50分别为4,5.2,22nM。Lenvatinib分别以51,39,46,100nM的IC50抑制PDGFRα,PDGFRβ,FGFR1和KIT[3]。

[体内研究]

甲磺酸Lenvatinib(E7080甲磺酸)(100mg/kg,p.o.)给药,贝伐单抗在m.f.p.显着抑制局部肿瘤生长,并且在治疗结束时,甲磺酸Lenvatinib也显着抑制局部淋巴结和远端肺的转移[3]。甲磺酸Lenvatinib(E7080甲磺酸盐)以剂量依赖性方式抑制30和100 mg/kg(BID,QDx21)下H146肿瘤的生长,并在H146异种移植模型中以100 mg/kg引起肿瘤消退。用抗CD31抗体进行IHC分析表明,与抗VEGF抗体和伊马替尼治疗相比,100 mg/kg的lenvatinib降低了微血管密度[4]。

[参考文献]

[1]. Kudo M, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellularcarcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173.

[2]. Suyama K, et al. Lenvatinib: A Promising Molecular Targeted Agent for Multiple Cancers. Cancer Control. 2018 Jan-Dec;25(1):1073274818789361.

[3]. 3.Matsui J, et al. 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, 14(17),545.

[4]. Matsui J, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008, 122(3), 664-671.