Organelle-specific Hsp90 inhibitors

被引:29
作者
Seo, Young Ho [1 ]
机构
[1] Keimyung Univ, Coll Pharm, Taegu 704701, South Korea
基金
新加坡国家研究基金会;
关键词
Heat shock protein 90; Extracellular matrix; Mitochondria; Organelle; Hsp90; inhibitors; CELL LUNG-CANCER; MITOCHONDRIAL PERMEABILITY TRANSITION; NECROSIS-FACTOR RECEPTOR; HEAT-SHOCK; CYCLOPHILIN-D; EXTRACELLULAR HSP90; PANCREATIC-CANCER; OXIDATIVE STRESS; PROSTATE-CANCER; DRUG DISCOVERY;
D O I
10.1007/s12272-015-0636-1
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone that is involved in the folding, activation, and stabilization of numerous oncogenic proteins. It has become an attractive therapeutic target, especially for eradicating malignant cancers and overcoming chemotherapy resistance. The Hsp90 family in mammalian cells is composed of four major homologs: Hsp90 alpha, Hsp90 beta, 94-kDa glucose-regulated protein (Grp94), and TNF receptor-associated protein 1 (Trap1). Hsp90 alpha and Hsp90 beta are mainly localized in the cytoplasm, while Grp94 and Trap1 reside in the endoplasmic reticulum and the mitochondria, respectively. Additionally, some Hsp90 s are secreted from the cytoplasm, commonly called extracellular Hsp90. Interestingly, each Hsp90 isoform is localized in a particular organelle, possesses a unique biological function, and participates in various physiological and pathological processes. To inhibit the organelle-specific Hsp90 chaperone function, there have been significant efforts to accumulate Hsp90 inhibitors in particular cellular compartments. This review introduces current studies regarding the delivery of Hsp90 inhibitors to subcellular organelles, particularly to the extracellular matrix and the mitochondria, and discusses their biological insights and therapeutic implications.
引用
收藏
页码:1582 / 1590
页数:9
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