Konstantinopoulos Panagiotis A, Papavassiliou Athanasios G
Expert Opin Investig Drugs. 2005 Dec;14(12):1471-4. doi: 10.1517/13543784.14.12.1471.
Heat-shock protein 90 (Hsp90) is a molecular chaperone involved in three-dimensional folding, intracellular translocation and degradation of multiple key regulatory proteins. Accumulated evidence has indicated an important role of Hsp90 in several signal transduction pathways that are deregulated in carcinogenesis. 17-allylamino-17-demethoxygeldanamycin (17-AAG), a selective inhibitor of Hsp90, is currently under clinical investigation in advanced malignancies in which Hsp90 client proteins are implicated. This article discusses the mechanistic evidence underlying 17-AAG's cytostatic, proapoptotic, antiangiogenic and anti-invasive properties that provide the basis for its antitumour activity and underscores its unique therapeutic potential as a multi-targeted agent, as opposed to most of the current-generation molecular therapeutics.
热休克蛋白90（Hsp90）是一种分子伴侣，参与多种关键调节蛋白的三维折叠、细胞内转运和降解。越来越多的证据表明，Hsp90在致癌过程中失调的几种信号转导途径中发挥重要作用。17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG）是Hsp90的一种选择性抑制剂，目前正在对涉及Hsp90客户蛋白的晚期恶性肿瘤进行临床研究。本文讨论了17-AAG的细胞生长抑制、促凋亡、抗血管生成和抗侵袭特性的机制证据，这些特性为其抗肿瘤活性提供了基础，并强调了其作为一种多靶点药物相对于大多数当代分子疗法而言独特的治疗潜力。
