如何选择VEGFR抑制剂?

VEGFR即血管内皮生长因子受体,包括三种亚型,VEGFR-1、VEGFR-2、VEGFR-3,其中VEGFR-2主要表达在血管内皮细胞,是VEGF(血管内皮生长因子)的主要受体。VEGF与VEGFR结合,通过一系列信号传导最终导致血管生成。

VEGFR抑制剂通过作用于VEGFR靶点,抑制下游信号通路,实现阻断血管生成的目的。据此多种VEGFR抑制剂被应用于肺癌、肝癌、肾癌等各种肿瘤研究及治疗中。

图1 肿瘤新生血管形成中的VEGF与VEGFR[1]

VEGFR抑制剂选择见下表:
注:1、IC50: 全称half maximal inhibitory concentration,指物质发挥其最大抑制效果的一半时的浓度。 2、代表抑制作用的强度,抑制作用越强, 越多。
  1. Giordano G , Febbraro A, Venditti M, etc. Targeting Angiogenesis and Tumor Microenvironment in Metastatic Colorectal Cancer:Role of Aflibercept. Gastroenterol Res Pract. 2014;2014:526178.
1020808
341031-54-7
Sunitinib malate, 98%
Description:
a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively
1109982
212141-51-0
Vatalanib dihydrochloride, 99%
Description:
an inhibitor of VEGFR2/KDR with IC50 of 37 nM
381939
557795-19-4
Sunitinib, 98%
Description:
a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively
812864
319460-85-0
Axitinib, 98%
Description:
an inhibitor of VEGFR2/KDR with IC50 of 37 nM
814262
443913-73-3
Vandetanib, 99%
Description:
a potent inhibitor of VEGFR2 with an IC50 of 40 nM
976408
755037-03-7
Regorafenib, 98%
Description:
a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively
981527
444731-52-6
Pazopanib, 98%
Description:
a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with IC50s of 10, 30, 47, 84, 74, 140 and 146 nM, respectively
1239124
943319-70-8
Ponatinib, 99%
Description:
a potent, orally available multi-targeted kinase inhibitor with IC50s of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively
1497607
1140909-48-3
Cabozantinib malate, 98%
Description:
a potent VEGFR2 inhibitor