Discovery of multi-target receptor tyrosine kinase inhibitors as novel anti-angiogenesis agents

被引：19

作者：

Wang, Jinfeng ^{[1
]}

Zhang, Lin ^{[1
]}

Pan, Xiaoyan ^{[1
]}

Dai, Bingling ^{[1
]}

Sun, Ying ^{[1
]}

Li, Chuansheng ^{[1
]}

Zhang, Jie ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Sch Pharm, Hlth Sci Ctr, 76 Yanta West Rd, Xian 710061, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

中国国家自然科学基金;

关键词：

VASCULAR NORMALIZATION; C-MET; DERIVATIVES; EXPLORATION; VEGFR2; DESIGN;

D O I：

10.1038/srep45145

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recently, we have identified a biphenyl-aryl urea incorporated with salicylaldoxime (BPS-7) as an anti-angiogenesis agent. Herein, we disclosed a series of novel anti-angiogenesis agents with BPS-7 as lead compound through combining diarylureas with N-pyridin-2-ylcyclopropane carboxamide. Several title compounds exhibited simultaneous inhibition effects against three pro-angiogenic RTKs (VEGFR-2, TIE-2 and EphB4). Some of them displayed potent anti-proliferative activity against human vascular endothelial cell (EA.hy926). In particular, two potent compounds (CDAU-1 and CDAU-2) could be considered as promising anti-angiogenesis agents with triplet inhibition profile. The biological evaluation and molecular docking results indicate that N-pyridin-2-ylcyclopropane carboxamide could serve as a hinge-binding group (HBG) for the discovery of multi-target anti-angiogenesis agents. CDAU-2 also exhibited promising anti-angiogenic potency in a tissue model for angiogenesis.

引用

页数：11

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