西地尼布马来酸盐

中文名称:

西地尼布马来酸盐

中文同义词:

西地尼布马来酸盐;西地尼布马来酸盐1;VEGFR2抑制剂(CEDIRANIB MALEATE)

英文名称:

Cediranib Maleate

英文同义词:

Cediranib Maleate;AZD 2171 Maleate;West to Ni BuMa Maleate;Cediranib Maleate(AZD-2171);4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline maleate;Cediranib maleate (AZD-2171 maleate;AZD-2171 MALEATE;AZD 2171 MALEATE

CAS号:

857036-77-2

分子式:

C25H27FN4O3·C4H4O4

分子量:

0

EINECS号:

相关类别:

抗肿瘤类药物及免疫抑制剂;医药类;细胞生物学试剂;API;API

Mol文件:

Mol File

熔点 

198.3-200.08 °C (polymorph)

生物活性

Cediranib maleate (AZD-2171 maleate) 是高选择性，有口服活性的 VEGFR2 抑制剂，对Flt1，KDR，Flt4，PDGFRα，PDGFRβ，c-Kit的 IC50 值分别为小于1， 小于3，5，5，36，2nM。

靶点

Target Value VEGFR2/KDR (HUVECs) 0.5 nM c-Kit (HUVECs) 2 nM c-Kit (HUVECs) 2 nM VEGFR3/FLT4 (HUVECs) <=3 nM VEGFR1/FLT1 (HUVECs) 5 nM

Target

Value

VEGFR2/KDR (HUVECs)

0.5 nM

c-Kit (HUVECs)

2 nM

c-Kit (HUVECs)

2 nM

VEGFR3/FLT4 (HUVECs)

<=3 nM

VEGFR1/FLT1 (HUVECs)

5 nM

体外研究

In human umbilical vein endothelial cells, Cediranib inhibits VEGF-stimulated proliferation and KDR phosphorylation with IC 50 values of 0.4 and 0.5 nM, respectively. In a fibroblast/endothelial cell coculture model of vessel sprouting, Cediranib also reduces vessel area, length, and branching at subnanomolar concentrations.

体内研究

Once-daily oral administration of Cediranib ablates experimental (VEGF-induced) angiogenesis and inhibits endochondral ossification in bone or corpora luteal development in ovary; physiologic processes that are highly dependent upon neovascularization. The growth of established human tumor xenografts (colon, lung, prostate, breast, and ovary) in athymic mice is inhibited dose-dependently by Cediranib, with chronic administration of 1.5 mg per kg per day producing statistically significant inhibition in all models. A histologic analysis of Calu-6 lung tumors treated with Cediranib reveals a reduction in microvessel density within 52 hours that becomes progressively greater with the duration of treatment. These changes are indicative of vascular regression within tumors.