Taldone Tony, Gozman Alexander, Maharaj Ronnie, Chiosis Gabriela
Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Curr Opin Pharmacol. 2008 Aug;8(4):370-4. doi: 10.1016/j.coph.2008.06.015. Epub 2008 Jul 31.
The Hsp90 multichaperone complex has important roles in the development and progression of malignant transformation. Several small-molecule inhibitors of Hsp90 of diverse chemotypes have shown potent antitumor activity in a wide-range of malignancies, and are currently in clinical or late-stage preclinical investigation. This review intends to update the reader on advances made over the past two years in the clinical development of Hsp90 inhibitors in advanced cancers. It will refer to the two 17-AAG formulations, tanespimycin and IPI-504, and to synthetic small molecules, among which are the purine-scaffold Hsp90 inhibitor CNF2024/BIIB021, the isoxazole derivative VER-52296/NVP-AUY922, and the carbazol-4-one benzamide derivative SNX-5422, and will present our current knowledge on their clinical performance.
热休克蛋白90（Hsp90）多分子伴侣复合物在恶性转化的发生和发展过程中发挥着重要作用。几种具有不同化学类型的Hsp90小分子抑制剂在多种恶性肿瘤中均显示出强大的抗肿瘤活性，目前正处于临床或临床前后期研究阶段。本综述旨在向读者介绍过去两年中Hsp90抑制剂在晚期癌症临床开发方面取得的进展。文中将提及两种17-AAG制剂（坦螺旋霉素和IPI-504）以及合成小分子，其中包括嘌呤骨架的Hsp90抑制剂CNF2024/BIIB021、异恶唑衍生物VER-52296/NVP-AUY922和咔唑-4-酮苯甲酰胺衍生物SNX-5422，并将展示我们目前对它们临床性能的了解。
