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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

VEGF Signal System: The Application of Antiangiogenesis

Author(s): Xuewu Liang, Fuming Xu, Xiaoguang Li, Chunhua Ma, Yingjie Zhang and Wenfang Xu

Volume 21, Issue 7, 2014

Page: [894 - 910] Pages: 17

DOI: 10.2174/09298673113206660264

Price: $65

Abstract

Among the numerous endogenous promoters of angiogenesis, vascular endothelia growth factor (VEGF) plays a leading role in angiogenesis, which has huge impact on proliferation, survival, migration and permeability of tumor cells. VEGF signal system also becomes remarkable anticancer targets, including VEGF, vascular endothelia growth factor receptor (VEGFR), and VEGF downstream signal pathways. So far, there has been many clinical or approved anticancer drugs that directly or indireactly interfere with VEGF signal system applied in the treatment of various tumors and other diseases associated with pathological angiogenesis. Various kinds of antiangiogenic agents which inhibit VEGF and VEGFR have been developed and discovered gradually, including antibodies, ribozymes and small molecule inhibitors. Meanwhile, the investigation into antiangiogenic agents which block certain signal proteins of VEGF downstream signal pathways attracts the attention of medicinal chemists and enriches the application of antiangiogenic agents. This review will interpret the mysterious VEGF signal system from its molecular structure and probe to the mechanism of the combination of VEGF and its receptors. Furthermore, the detail of VEGF signal pathways will be introduced comprehensively and methodically. In addition, some up-to-date clinical or approved anticancer agents will be clearly tabulated. The binding modes of different kinase inhibitors will be used to explain the SAR of the small molecule inhibitors. Finally, in order to make the readers master VEGF signal system completely, some novel targets and inhibitors which block the downstream signal pathways of VEGF are plainly stated.

Keywords: Anticancer agents, kinase inhibitors, signal pathways, VEGF, VEGFR.


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