Recent Advances in the Design and Synthesis of c-Met Inhibitors as Anticancer Agents (2014-Present)

被引:8
作者
Lv, Peng-Cheng [1 ]
Wang, Zhong-Chang [1 ]
Zhu, Hai-Liang [1 ]
机构
[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
c-Met inhibitors; hepatocyte growth factor receptor (HGFR); ATP-competitive inhibitors; anticancer agents; structure-activity relationship analysis; binding modes; RECEPTOR TYROSINE KINASE; DISCOVERY; CANCER; RESISTANCE; OPTIMIZATION; GROWTH; IDENTIFICATION; GEFITINIB; POTENT; SERIES;
D O I
10.2174/0929867323666161028161441
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:57 / 64
页数:8
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