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靶向动态微管的药物:一种新的分子视角。

Drugs that target dynamic microtubules: a new molecular perspective.

机构信息

Department of Biology, Georgia State University, Atlanta, USA.

出版信息

Med Res Rev. 2011 May;31(3):443-81. doi: 10.1002/med.20242. Epub 2011 Mar 4.

Abstract

Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These "biological vectors" can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.

摘要

微管一直被认为是抗癌药物的理想靶点,因为它们在有丝分裂中发挥着重要作用,形成动态的纺锤体装置。因此,目前有许多不同的化合物正在临床使用和开发中,它们通过改变微管动力学作为抗有丝分裂剂发挥作用。尽管这些不同的分子在与三个已建立的药物结构域(紫杉烷、长春花生物碱或秋水仙碱结合)之一结合时已知会影响微管动力学,但每种药物的确切作用机制仍然是一个激烈推测和研究的领域。在这项研究中,我们从一个新的角度回顾了微管结合化疗药物的作用,考虑了它们的结合方式如何诱导构象变化,并改变了相对于微管组装或解组装的分子载体的生物学功能。因此,这些“生物载体”可以用作描述微管靶向药物作用的分子机制的时空背景。

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