Lv Peng-Cheng, Wang Zhong-Chang, Zhu Hai-Liang
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Curr Med Chem. 2017;24(1):57-64. doi: 10.2174/0929867323666161028161441.
c-Met, also known as the surface receptor of hepatocyte growth factor receptor (HGFR), is a receptor tyrosine kinase with heterodimer transmembrane. c-Met involves in the activation of several signaling pathways, most of them are implicated in aggressive cancer phenotypes. In a variety of human malignances, c-Met/HGF signaling has been found aberrant, and in many instances, has been correlated with advanced disease stage and poor prognosis. Thus, the c-Met has identified as an emerging and interesting target for cancer chemotherapy. In this review, we briefly summarize signaling pathways of c-Met, and discuss the crystal structures of representative c-Met and the binding modes with their ligands. We also present updates on the design, synthesis and structure-activity relationship analysis of c-Met inhibitors developed from 2014 till now. At last, we review the c-Met inhibitors that are in clinical development and highlight the future prospects.
c-Met，也被称为肝细胞生长因子受体（HGFR）的表面受体，是一种具有异二聚体跨膜结构的受体酪氨酸激酶。c-Met参与多种信号通路的激活，其中大多数与侵袭性癌症表型有关。在多种人类恶性肿瘤中，已发现c-Met/HGF信号异常，并且在许多情况下，与疾病晚期和预后不良相关。因此，c-Met已被确定为癌症化疗中一个新兴且有趣的靶点。在本综述中，我们简要总结了c-Met的信号通路，并讨论了代表性c-Met的晶体结构及其与配体的结合模式。我们还介绍了2014年至今开发的c-Met抑制剂的设计、合成及构效关系分析的最新进展。最后，我们综述了正在进行临床开发的c-Met抑制剂，并突出了未来前景。
