乙酰肝素酶靶点药物的抗肿瘤活性研究进展

Advancement of antineoplastic activity research on heparanase drugs

乙酰肝素酶是葡萄糖醛酸内切酶,通过水解细胞膜和细胞外基质的重要组成成分-硫酸乙酰肝素,释放出促生长因子,有利于肿瘤细胞的侵袭和转移。以乙酰肝素酶作为抗癌药物靶点的一系列半合成多糖类、合成小分子类和天然产物类化合物陆续被发现出来,其PI-88已经进入临床研究阶段。另外乙酰肝素酶的晶体结构也已经成功得到解析,使基于蛋白结构的理性药物设计成为可能。本文系统的介绍了乙酰肝素酶抑制剂抗肿瘤活性研究进展。

Heparanase is a glucuronic acid en- zyme, it hydrolizes heparin sulfate, which is main components of cell membrane and extracel- lular matrix, growth factors are released to pro- mote tumor cell invasion and metastasis. As for the antineoplastic drug targets, a series of poly- saccharides, synthetic small chemical compounds and natural product compounds have been found, some of them have begin the clinical re- search. The crystal structures of heparanasehave successfully been discovered, so it is possi- ble to do rational drug design based on 3D pro- tein structures. This paper introduces antineo- plastic activity research advance of heparanase inhibitors in details.