Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; Warren Family Research Center for Drug Discovery and Development, University of Notre Dame, Notre Dame, IN 46556, USA.
Bioorg Med Chem Lett. 2023 Jan 15;80:129111. doi: 10.1016/j.bmcl.2022.129111. Epub 2022 Dec 19.
Heat shock protein 90 (Hsp90) is a dynamic protein which serves to ensure proper folding of nascent client proteins, regulate transcriptional responses to environmental stress and guide misfolded and damaged proteins to destruction via ubiquitin proteasome pathway. Recent advances in the field of Hsp90 have been made through development of isoform selective inhibitors, Hsp90 C-terminal inhibitors and disruption of protein-protein interactions. These approaches have led to alleviation of adverse off-target effects caused by pan-inhibition of Hsp90 using N-terminal inhibitors. In this review, we provide an overview of relevant advances on targeting the Hsp90 C-terminal Domain (CTD) and the development of Hsp90 C-terminal inhibitors (CTIs) since 2015.
热休克蛋白 90（Hsp90）是一种动态蛋白，它的功能是确保新生客户蛋白的正确折叠，调节对环境压力的转录反应，并通过泛素蛋白酶体途径引导错误折叠和受损的蛋白进行破坏。Hsp90 领域的最新进展是通过开发同工型选择性抑制剂、Hsp90 C 端抑制剂和破坏蛋白-蛋白相互作用来实现的。这些方法减轻了使用 N 端抑制剂对 Hsp90 进行泛抑制所引起的不良脱靶效应。在这篇综述中，我们提供了自 2015 年以来针对 Hsp90 C 端结构域（CTD）和 Hsp90 C 端抑制剂（CTIs）开发的相关进展概述。
