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.
Keywords: c-Met inhibitors, hepatocyte growth factor receptor (HGFR), ATP-competitive inhibitors, anticancer
agents, structure-activity relationship analysis, binding modes.
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