硫酸乙酰肝素酶(HPSE)抑制剂的研究进展  

Research progress of HPSE inhibitors

作　　者：毕文敬 江建冰 BI Wen-jing;JIANG Jian-bing(School of Pharmacy,Shenzhen University,Shenzhen 518000,China;Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518000,China)

机构地区：[1]深圳大学药学院,广东深圳518000 [2]中国科学院深圳先进技术研究院,广东深圳518000

出　　处：《中国药物化学杂志》2022年第3期231-244,共14页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(21807106);广东省自然科学基金博士启动项目(2018A030310035);深圳市科创委基础研究自由探索项目(JCYJ20180302145723601)。

摘　　要：硫酸乙酰肝素酶(heparanase,HPSE)是一种参与细胞外基质(extracellular matrix,ECM)重塑的关键酶,可降解硫酸乙酰肝素(heparan sulfate,HS)和硫酸乙酰肝素蛋白聚糖(heparan sulfate proteoglycan,HSPG),破坏和改变细胞外基质和基底膜(basement membrane,BM)结构,从而促进肿瘤细胞的侵袭和转移,其表达的升高与肿瘤和肾脏纤维化等疾病有关。另外,乙酰肝素酶还可以通过增强自噬来促进肿瘤细胞生长和化疗耐药,在抗肿瘤治疗中,硫酸乙酰肝素酶已经是一个被证实的靶点。本文作者根据抑制剂的结构和来源进行分类,综述了近些年来的硫酸乙酰肝素酶的抑制剂,以期为靶向乙酰肝素酶的抑制剂筛选与开发提供借鉴和参考。Heparanase(HPSE)is a key enzyme involved in the remodeling of the extracellular matrix(ECM),degrading heparin-sulphate-proteoglycans(HS)and heparin sulfate proteoglycan(HSPG).It can break down the structure of extracellular matrix(ECM)and basement membrane(BM).It promotes the invasion and metastasis of tumor cells,and the increase of its expression is related to diseases such as tumor and kidney fibrosis.In addition,heparanase can promote the growth of tumor cell and chemotherapy resistance by promoting autophagy.Heparanase is a known target in antitumor therapy.In this review,HPSE inhibitors in recent years are summarized by classifying them according to their structure and source,it is expected to provide useful reference and suggestion for the screening and development of inhibitors towards heparanase.

关 键 词：化学生物学 硫酸乙酰肝素酶 硫酸乙酰肝素蛋白聚糖 抑制剂 肾纤维化 TGF-Β 生长因子 

分 类 号：R914[医药卫生—药物化学]