Department of Medicinal Chemistry Key Laboratory of Chemical Biology (Ministry of Education) School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, 250012, PR China.
Department of Medicinal Chemistry Key Laboratory of Chemical Biology (Ministry of Education) School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, 250012, PR China.
Eur J Med Chem. 2016 Oct 4;121:209-220. doi: 10.1016/j.ejmech.2016.05.052. Epub 2016 May 24.
Heparanase, an only endo-β-d-glucuronidase capable of cleaving heparan sulfate (HS) side chains at specific sites, contributes to remodeling of the extracellular matrix (ECM) and releasing of HS-linked growth factors, cytokines and signaling proteins. In addition, heparanase also plays an indispensable role in tumor angiogenesis, invasion and metastasis, indicating that it is a promising target for the development of antitumor drugs. Recent progress leads to three classes of heparanase inhibitors, including active analogs of endogenous substance, synthetic small molecule compounds and natural products. In this review, following an outline on the heparanase structure and function, an overview of the advancement of heparanase inhibitors as novel and potent anti-cancer agents will be given, especially introducing various existing heparanase inhibitors, as well as their inhibitory activities and mechanisms of action.
乙酰肝素酶是唯一能够在特定位点切割硫酸乙酰肝素（HS）侧链的内切β-D-葡糖醛酸酶，有助于细胞外基质（ECM）的重塑和 HS 连接的生长因子、细胞因子和信号蛋白的释放。此外，乙酰肝素酶在肿瘤血管生成、侵袭和转移中也起着不可或缺的作用，这表明它是开发抗肿瘤药物的一个有前途的靶点。最近的研究进展产生了三类乙酰肝素酶抑制剂，包括内源性物质的活性类似物、合成小分子化合物和天然产物。在这篇综述中，在概述乙酰肝素酶的结构和功能之后，将介绍作为新型强效抗癌药物的乙酰肝素酶抑制剂的研究进展，特别介绍各种现有的乙酰肝素酶抑制剂及其抑制活性和作用机制。
