Institut für Organische Chemie und Zentrum für Biomolekulare Wirkstoffchemie (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, D-30167 Hannover, Germany.
Nat Prod Rep. 2013 Oct 11;30(10):1299-323. doi: 10.1039/c3np70012g. Epub 2013 Aug 12.
Covering 2005 to 2013. In this review recent progress in the development of heat shock proteins (Hsp90) in oncogenesis is illuminated. Particular emphasis is put on inhibitors such as geldanamycin and analogues that serve as a natural product show case. Hsp90 has emerged as an important target in cancer therapy and/or against pathogenic cells which elicit abnormal Hsp patterns. Competition for ATP by geldanamycin and related compounds abrogate the chaperone function of Hsp90. In this context, this account pursues three topics in detail: a) Hsp90 and its biochemistry, b) Hsp90 and its role in oncogenesis and c) strategies to create compound libraries of structurally complex inhibitors like geldanamycin on which SAR studies and the development of drugs that are currently in different stages of clinical testing rely.
涵盖 2005 年至 2013 年。在这篇综述中，阐述了热休克蛋白（Hsp90）在肿瘤发生过程中的最新进展。特别强调了抑制剂，如格尔德霉素及其类似物，它们是天然产物的典范。Hsp90 已成为癌症治疗和/或针对异常 Hsp 模式的致病细胞的重要靶点。格尔德霉素和相关化合物通过与 ATP 的竞争，使 Hsp90 的伴侣功能丧失。在这方面，本报告详细探讨了三个主题：a）Hsp90 及其生物化学，b）Hsp90 在肿瘤发生中的作用，以及 c）构建结构复杂抑制剂化合物库的策略，如格尔德霉素，这些抑制剂化合物库是基于 SAR 研究和药物开发的，目前处于不同的临床测试阶段。
