Discovery of Dual VEGFR-2 and Tubulin Inhibitors with in Vivo Efficacy

被引：24

作者：

Chekler, Eugene L. Piatnitski ^{[1
]}

Kiselyov, Alexander S. ^{[1
]}

Ouyang, Xiaohu ^{[1
]}

Chen, Xiaoling ^{[1
]}

Pattaropong, Vatee ^{[1
]}

Wang, Ying ^{[2
]}

Tuma, M. Carolina ^{[2
]}

Doody, Jacqueline F. ^{[2
]}

机构：

[1] ImClone Syst, Dept Chem, New York, NY 10014 USA

[2] ImClone Syst, Dept Cell Biol, New York, NY 10014 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2010年 / 1卷 / 09期

关键词：

Tubulin; angiogenesis; VEGFR; tumor vasculature; antimitotic; vascular disrupting agent; POTENT INHIBITORS;

D O I：

10.1021/ml1001568

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In an effort to develop potent, orally bioavailable compounds for the treatment of neoplastic diseases, we developed a class of dual VEGFR-2 kinase and tubulin inhibitors. Targeting the VEGFR receptor kinase and tubulin structure allows for inhibition of both tumor cells and tumor vasculature. Previously, a combination of two compounds, a VEGF receptor tyrosine kinase inhibitor and tubulin agent, was demonstrated to produce an enhanced antitumor response in animal studies. We have reaffirmed their results, with the added benefit that both activities are found in one compound.

引用

页码：488 / 492

页数：5

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