Recent Advances in the Design and Synthesis of c-Met Inhibitors as Anticancer Agents (2014-Present).
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.
Peng-Cheng
PC
Lv
Zhong-Chang
ZC
Wang
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Hai-Liang
HL
Zhu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D008024:Ligands; D047428:Protein Kinase Inhibitors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
ATP-competitive inhibitors; anticancer
agents; binding modes; c-Met inhibitors; hepatocyte growth factor receptor (HGFR); structure-activity relationship analysis