Natural Product Inspired N-Terminal Hsp90 Inhibitors: From Bench to Bedside?
Natural Product Inspired N-Terminal Hsp90 Inhibitors: From Bench to Bedside?
复制标题
DOI：
10.1002/med.21351
复制
发表时间：
2016-01
影响因子：
13.3
通讯作者：
Blagg BSJ
中科院分区：
文献类型：
--
作者：
Khandelwal A;Crowley VM;Blagg BSJ
90 kDa热休克蛋白(Hsp90)负责新生多肽的构象成熟和变性蛋白的再成熟。依赖于Hsp90的蛋白质与癌症的所有六个特征都有关。当Hsp90被抑制时，蛋白质底物通过泛素-蛋白酶体途径降解。因此，抑制Hsp90为癌症的治疗提供了一个治疗机会。Hsp90的天然产物抑制剂已经在体外被确定，这已经成为开发更有效的抑制剂和类似物的先导，这些抑制剂和类似物已经进入临床试验。本综述重点介绍了天然产物类似物的开发，以及从天然产物中产生的具有临床重要性的抑制剂的开发。
The 90 kDa heat shock proteins (Hsp90) are responsible for the conformational maturation of nascent polypeptides and the rematuration of denatured proteins. Proteins dependent upon Hsp90 are associated with all six hallmarks of cancer. Upon Hsp90 inhibition, protein substrates are degraded via the ubiquitin-proteasome pathway. Consequentially, inhibition of Hsp90 offers a therapeutic opportunity for the treatment of cancer. Natural product inhibitors of Hsp90 have been identified in vitro, which have served as leads for the development of more efficacious inhibitors and analogs that have entered clinical trials. This review highlights the development of natural product analogs, as well as the development of clinically important inhibitors that arose from natural products.