Hsp90 抑制：消除休克和应激。
Hsp90 inhibition: elimination of shock and stress.
机构信息
Department of Medicinal Chemistry, The University of Kansas, Kansas, USA.
出版信息
Bioorg Med Chem Lett. 2010 Sep 1;20(17):4983-7. doi: 10.1016/j.bmcl.2010.06.108. Epub 2010 Jul 1.
Abstract
The 90 kDa heat shock proteins (Hsp90) represent a class of molecular chaperones responsible for the maturation and stabilization of many oncogenic proteins. Disrupting the ability of ATP to bind and facilitate the operation of Hsp90 has emerged as a promising approach toward cancer chemotherapeutic development. While numerous Hsp90 inhibitory scaffolds have been identified, progress through the clinic has revealed many obstacles that should be addressed in future analogue development. Recent reports of the complications, pitfalls, and downstream effects associated with Hsp90 inhibition are discussed herein, in hopes of providing a reference that can be used to guide the future design of Hsp90 inhibitory scaffolds.
摘要
90kDa 热休克蛋白（Hsp90）是一类分子伴侣，负责许多致癌蛋白的成熟和稳定。破坏 ATP 结合并促进 Hsp90 运作的能力已成为癌症化疗开发的一种有前途的方法。虽然已经确定了许多 Hsp90 抑制性支架，但临床进展揭示了许多在未来类似物开发中需要解决的障碍。本文讨论了与 Hsp90 抑制相关的并发症、陷阱和下游效应的最新报道，希望能提供一个参考，用于指导 Hsp90 抑制性支架的未来设计。
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