HSP90 (heat shock protein 90) is an ATP-dependent molecular chaperone involved in a proper folding and maturation of hundreds of proteins. HSP90 is abundantly expressed in cancer, including melanoma. HSP90 client proteins are the key oncoproteins of several signaling pathways controlling melanoma development, progression and response to therapy. A number of natural and synthetic compounds of different chemical structures and binding sites within HSP90 have been identified as selective HSP90 inhibitors. The majority of HSP90-targeting agents affect N-terminal ATPase activity of HSP90. In contrast to N-terminal inhibitors, agents interacting with the middle and C-terminal domains of HSP90 do not induce HSP70-dependent cytoprotective response. Several inhibitors of HSP90 were tested against melanoma in pre-clinical studies and clinical trials, providing evidence that these agents can be considered either as single or complementary therapeutic strategy. This review summarizes current knowledge on the role of HSP90 protein in cancer with focus on melanoma, and provides an overview of structurally different HSP90 inhibitors that are considered as potential therapeutics for melanoma treatment.

中文翻译：

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HSP90在黑色素瘤中的抑制剂。

HSP90（热激蛋白90）是一种ATP依赖性分子伴侣，参与数百种蛋白的正确折叠和成熟。HSP90在包括黑素瘤在内的癌症中大量表达。HSP90客户蛋白是控制黑色素瘤发展，进程和对治疗反应的几种信号通路的关键癌蛋白。HSP90中许多具有不同化学结构和结合位点的天然和合成化合物已被鉴定为选择性HSP90抑制剂。大多数HSP90靶向剂会影响HSP90的N末端ATPase活性。与N末端抑制剂相反，与HSP90的中部和C末端结构域相互作用的药物不会诱导HSP70依赖性的细胞保护反应。在临床前研究和临床试验中对HSP90的几种抑制剂进行了针对黑色素瘤的测试，提供证据表明这些药物可被视为单一或辅助治疗策略。这篇综述总结了关于HSP90蛋白在癌症中对黑素瘤的作用的当前知识，并概述了结构上不同的HSP90抑制剂，这些抑制剂被认为是黑素瘤治疗的潜在疗法。