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驱动蛋白纺锤体蛋白抑制剂作为抗癌药物的研究进展

Progress on kinesin spindle protein inhibitors as anti-cancer agents.

作者信息

Zhang Yingjie, Xu Wenfang

机构信息

Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, China.

出版信息

Anticancer Agents Med Chem. 2008 Aug;8(6):698-704.

Abstract

The kinesin spindle protein (KSP, also known as Hs Eg5) plays an essential part in the proper separation of spindle poles and the correct formation of bipolar mitotic spindle during mitosis. Inhibition of this protein results in cells apoptosis followed by mitotic arrest and the formation of characteristic monoaster spindles. Compared with the traditional chemotherapeutic agents (taxanes, vinca alkaloids), KSP inhibitors (KSPi) will not lead to the neuropathic side effects, so KSP has become a novel and an attractive anticancer target. Accordingly, more and more interest has been focused on the development of high effective and selective KSPi. This review will focus on some kinds of KSPi on the basis of introducing structure and function of KSP.

摘要

驱动蛋白纺锤体蛋白(KSP,也称为Hs Eg5)在有丝分裂过程中纺锤体极的正确分离和双极有丝分裂纺锤体的正确形成中起着至关重要的作用。抑制这种蛋白质会导致细胞凋亡,随后发生有丝分裂停滞并形成特征性的单星纺锤体。与传统化疗药物(紫杉烷类、长春花生物碱)相比,KSP抑制剂(KSPi)不会导致神经病变副作用,因此KSP已成为一个新的且有吸引力的抗癌靶点。相应地,越来越多的关注集中在开发高效且选择性的KSPi上。本综述将在介绍KSP的结构和功能的基础上,重点关注某些种类的KSPi。

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