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化学进展 2011, Vol. 23 Issue (8): 1683-1691 前一篇   后一篇

• 综述与评论 •

尿激酶(uPA)化学合成抑制剂

李永东*, 王华, 曾丹, 郭道义, 李勋, 范小林   

  1. 赣南师范学院化学与生命科学学院 江西省有机药物化学重点实验室 赣州 341000
  • 收稿日期:2010-11-01 修回日期:2011-01-01 出版日期:2011-08-24 发布日期:2011-07-25
  • 通讯作者: 李永东 E-mail:ydli2005@gmail.com
  • 基金资助:

    国家自然科学基金项目(No.30860073)和江西省自然科学基金项目(No.2008GQH0017)资助

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Synthetic Inhibitors of uPA

Li Yongdong*, Wang Hua, Zeng Dan, Guo Daoyi, Li Xun, Fan Xiaolin   

  1. Key Laboratory of Organo-Pharmaceutical Chemistry, Jiangxi Province, Gannan Normal University, Ganzhou 341000, China
  • Received:2010-11-01 Revised:2011-01-01 Online:2011-08-24 Published:2011-07-25

胞外蛋白的水解是恶性肿瘤细胞侵袭和转移的必要条件,各种蛋白酶的水解反应降解细胞外基质,破坏细胞/细胞间的联系以适应细胞的迁移。尿激酶型纤溶酶原激活物(尿激酶,urokinase-type plasminogen activator, uPA)激活不具有丝氨酸蛋白酶活性的纤溶酶原为活性纤溶酶,在保持血流畅通与防止血栓的形成中具有重要的作用。此外,活性尿激酶降解细胞外基质,激活多种基质金属蛋白酶,以适应肿瘤细胞的侵袭、扩散和转移。抑制尿激酶的活性被公认为是抑制癌症转移的有效方法,其中合成小分子uPA抑制剂成为抗癌治疗中的新理念。本文综述了合成uPA抑制剂的研究现状。

关键词： 尿激酶(uPA), 合成抑制剂, 丝氨酸蛋白酶, 肿瘤

The extracellular proteolysis is the necessary condition for the malignant process of tumor invasion and metastasis. These proteolytic reactions destruct the cell-cell and cell/ECM contacts and degrade the extracellular matrix (ECM) components which pose physical obstacle in the direction of migration/invasion. Urokinase-type plasminogen activator (uPA), which can activate the inactive plasminogen to plasmin, plays a pivotal role in clot lysis and keeps the blood flowing. Moreover, active uPA degrades ECM and activates a number of matrix metalloproteases, beginning a cascade of events adapting to the cancer cell invasion, spread and metastasis. The inhibition of uPA activity has been recognized as an efficient method in the treatment of cancer by retarding tumor growth and metastasis and inhibition of urokinase with synthetic inhibitor is a new concept for specific cancer therapy. Here we review the current research status of synthetic uPA inhibitors.

Contents
1 Introduction
2 Active positions of uPA serine protease domain (SPD)
3 Synthetic inhibitors of uPA
3.1 Non-peptidic inhibitors
3.2 Peptidic inhibitor
3.3 Other uPA inhibitors
4 Research status of uPA synthetic inhibitors in animal experiment
5 Prospects

Key words: uPA, synthetic inhibitors, serine protease, tumor

中图分类号: 

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尿激酶(uPA)化学合成抑制剂