College of Chemistry, Fuzhou University, Fuzhou, 350116, Fujian, People's Republic of China.
Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61 Biopolis Dr, 138673, Singapore, Singapore.
Cancer Metastasis Rev. 2019 Sep;38(3):507-524. doi: 10.1007/s10555-019-09802-8.
Matriptase is a type II transmembrane serine protease, which has been suggested to play critical roles in numerous pathways of biological developments. Matriptase is the activator of several oncogenic proteins, including urokinase-type plasminogen activator (uPA), hepatocyte growth factor (HGF) and protease-activated receptor 2 (PAR-2). The activations of these matriptase substrates subsequently lead to the generation of plasmin, matrix metalloproteases (MMPs), and the triggers for many other signaling pathways related to cancer proliferation and metastasis. Accordingly, matriptase is considered an emerging target for the treatments of cancer. Thus far, inhibitors of matriptase have been developed as potential anti-cancer agents, which include small-molecule inhibitors, peptide-based inhibitors, and monoclonal antibodies. This review covers established literature to summarize the chemical and biochemical aspects, especially the inhibitory mechanisms and structure-activity relationships (SARs) of matriptase inhibitors with the goal of proposing the strategies for their future developments in anti-cancer therapy.
组织蛋白酶 G 是一种 II 型跨膜丝氨酸蛋白酶，被认为在许多生物发育途径中发挥关键作用。组织蛋白酶 G 是几种致癌蛋白的激活剂，包括尿激酶型纤溶酶原激活物 (uPA)、肝细胞生长因子 (HGF) 和蛋白酶激活受体 2 (PAR-2)。这些组织蛋白酶 G 底物的激活随后导致纤溶酶、基质金属蛋白酶 (MMPs) 的产生，以及与癌症增殖和转移相关的许多其他信号通路的触发。因此，组织蛋白酶 G 被认为是癌症治疗的一个新兴靶点。到目前为止，已经开发出组织蛋白酶 G 的抑制剂作为潜在的抗癌药物，包括小分子抑制剂、基于肽的抑制剂和单克隆抗体。本综述涵盖了已建立的文献，总结了组织蛋白酶 G 抑制剂的化学和生化方面，特别是其抑制机制和结构-活性关系 (SAR)，旨在为其在癌症治疗中的未来发展提出策略。
