Recent Progress in the Development of Small Molecule c-Met Inhibitors

Curr Top Med Chem. 2019;19(15):1276-1288. doi: 10.2174/1568026619666190712205353.

Abstract

C-Met, also referred to as Hepatocyte Growth Factor Receptor (HGFR), is a heterodimeric receptor tyrosine kinase. It has been determined that c-Met gene mutations, overexpression, and amplification also occur in a variety of human tumor types, and these events are closely related to the aberrant activation of the HGF/c-Met signaling pathway. Meanwhile, high c-Met expression is closely associated with poor prognosis in cancer patients. The c-Met kinase has emerged as an attractive target for developing antitumor agents. In this review, we cover the recent advances on the small molecule c-Met inhibitors discovered from 2018 until now, with a main focus on the rational design, synthesis and structureactivity relationship analysis.

Keywords: Anticancer agents; Drug development; Small molecule inhibitors; Structure-activity relationship analysis; Tyrosine kinase; c-Met..

Publication types

  • Review

MeSH terms

  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / metabolism
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*

Substances

  • Protein Kinase Inhibitors
  • Small Molecule Libraries
  • Proto-Oncogene Proteins c-met