大学化学 >> 2019, Vol. 34 >> Issue (7): 60-66.doi: 10.3866/PKU.DXHX201812025

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泛素-蛋白酶体与药物应用

刘扬*()   

  • 收稿日期:2018-12-31 录用日期:2019-04-16 发布日期:2019-04-25
  • 通讯作者: 刘扬 E-mail:yliu442@tsinghua.edu.cn
  • 基金资助:
    国家重点研发计划(2017YFA0505200);清华大学2017年秋本科教学改革项目

Ubiquitin-Proteasome Related Drug Applications

Yang LIU*()   

  • Received:2018-12-31 Accepted:2019-04-16 Published:2019-04-25
  • Contact: Yang LIU E-mail:yliu442@tsinghua.edu.cn
  • Supported by:
    国家重点研发计划(2017YFA0505200);清华大学2017年秋本科教学改革项目

摘要:

泛素-蛋白酶体通路是"消化"细胞内蛋白质的重要途径之一。作为体内的"清洁工",它通过降解不能正常工作的或者无用的蛋白质来维持细胞的正常功能。泛素-蛋白酶体通路调控多个重要的生命活动,如细胞增殖、分化、凋亡、DNA修复等。目前已报道的多种人类疾病与蛋白酶体通路的异常有关。经批准的蛋白酶体抑制剂也已成功用于治疗多发性骨髓瘤、套细胞淋巴瘤等癌症,而正在开发的多个靶向泛素-蛋白酶体通路不同组分的药物,如去泛素化酶抑制剂等临床前测试药物,泛素化酶调节剂、新的蛋白酶体抑制剂等临床试验药物等也显现出更值得期待的疗效。本文简要介绍了与泛素-蛋白酶体通路相关的药物研发应用。

关键词: 泛素-蛋白酶体通路, 癌症, 药物研发, 蛋白酶体抑制剂

Abstract:

In eukaryotes, the ubiquitin-proteasome pathway degrades the majority of intracellular proteins tagged with polyubiquitin chains. It participates in regulation of key cellular activities, such as cell proliferation, cell differentiation, apoptosis, DNA repair, etc. through the degradation of malformed or misfolded proteins. Dysfunctions of the ubiquitin-proteasome pathway have been linked to many diseases, including cancer and neurodegeneration, etc. The commercially available proteasome inhibitors have been successfully used to treat multiple myeloma and mantle cell lymphoma. In addition, novel inhibitors against other components of the ubiquitin-proteasome pathway, such as those enzymes that drive ubiquitination and deubiquitination in preclinical testing or clinical trials, exhibit promising therapeutic effects in vivo. This paper briefly introduces the ubiquitin-proteasome pathway related drug discovery progress.

Key words: Ubiquitin-proteasome pathway, Cancer, Drug development, Proteasome inhibitor

MSC2000: 

  • G64