Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Computer and Information Science, Indiana University Purdue University, Indianapolis, IN 46202, USA.
Drug Discov Today. 2017 Oct;22(10):1466-1477. doi: 10.1016/j.drudis.2017.05.009. Epub 2017 May 31.
Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is overexpressed in cells of almost all cancers but not in most normal tissues in adults. Survivin expression is required for cancer cell survival and knocking down its expression or inhibiting its function using molecular approaches results in spontaneous apoptosis. Thus, survivin is an attractive and perhaps ideal target for cancer drug discovery. However, a US Food and Drug Administration (FDA)-approved drug targeting survivin has yet to emerge. In this Foundation Review, we examine and evaluate various strategies that have been used to target survivin and the stages of each survivin inhibitor to help understand this lack of success. We also provide future perspectives moving forward in targeting survivin for drug discovery.
Survivin 是凋亡抑制蛋白 (IAP) 家族中最小的成员,几乎在所有癌症细胞中过度表达,但在大多数成人正常组织中不表达。Survivin 的表达是癌细胞存活所必需的,通过分子方法敲低其表达或抑制其功能会导致自发凋亡。因此,Survivin 是癌症药物发现的一个有吸引力的、或许是理想的靶点。然而,一种针对 Survivin 的美国食品和药物管理局 (FDA) 批准的药物尚未出现。在本综述中,我们检查和评估了用于靶向 Survivin 的各种策略以及每种 Survivin 抑制剂的阶段,以帮助理解这一缺乏成功的原因。我们还为针对 Survivin 进行药物发现提供了未来的展望。