摘要
生存素,凋亡抑制蛋白家族的一员,在绝大多数人类肿瘤细胞中高度表达,但在晚期分化的正常组织中表达很低或检测不到。生存素已被证明能够抑制癌症细胞凋亡,并促进细胞增殖。生存素的过度表达与肿瘤进展和耐药性密切相关。因为它在肿瘤细胞形成和维护的关键作用,生存素被认为是抗癌治疗的一个理想的目标物。然而,小分子存活素抑制剂的发展中受到的挑战来源于混乱的蛋白质-蛋白质之间关系。目前只有一小部分的生存素抑制剂是近期开发的,并且大多数这些抑制剂通过与其他生物分子相互作用而不是直接与生存素蛋白相互作用来减少生存素水平。尽管存在这些挑战,但发展强有力的和选择性小分子存活素抑制剂都是重要的,无论在基础科学还是更好地理解生存素生物学抑或是在转化研究开发可能更有效的广谱抗癌剂方面。在此综述中,对生存素的功能及其在癌症方面的作用进行了总结。最近的事态发展、挑战和小分子存活素抑制剂的未来方向也进行了详细的讨论。
关键词: BIRC5抑制剂,抑制细胞凋亡的蛋白,蛋白与蛋白相互作用抑制剂,小分子抗癌剂,存活素和癌症,存活素抑制剂。
Current Medicinal Chemistry
Title:Recent Advances on Small-Molecule Survivin Inhibitors
Volume: 22 Issue: 9
Author(s): Min Xiao and Wei Li
Affiliation:
关键词: BIRC5抑制剂,抑制细胞凋亡的蛋白,蛋白与蛋白相互作用抑制剂,小分子抗癌剂,存活素和癌症,存活素抑制剂。
摘要: Survivin, a member of the inhibitor of apoptosis proteins family, is highly expressed in most human neoplasms, but its expression is very low or undetectable in terminally differentiated normal tissues. Survivin has been shown to inhibit cancer cell apoptosis and promote cell proliferation. The overexpression of survivin closely correlates with tumor progression and drug resistance. Because of its key role in tumor formation and maintenance, survivin is considered as an ideal target for anticancer treatment. However, the development of small-molecule survivin inhibitors has been challenging due to the requirement to disrupt the protein-protein interactions. Currently only a limited number of survivin inhibitors have been developed in recent years, and most of these inhibitors reduce survivin levels by interacting with other biomolecules instead of directly interacting with survivin protein. Despite these challenges, developing potent and selective small-molecule survivin inhibitors will be important both in basic science to better understand survivin biology and in translational research to develop potentially more effective, broad-spectrum anticancer agents. In this review, the functions of survivin and its role in cancer are summarized. Recent developments, challenges, and future direction of small-molecule survivin inhibitors are also discussed in detail.
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Cite this article as:
Min Xiao and Wei Li , Recent Advances on Small-Molecule Survivin Inhibitors, Current Medicinal Chemistry 2015; 22 (9) . https://dx.doi.org/10.2174/0929867322666150114102146
DOI https://dx.doi.org/10.2174/0929867322666150114102146 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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