Inhibitors targeting hepatocyte growth factor receptor and their potential therapeutic applications

Abstract

The hepatocyte growth factor (HGF)/c-Met signaling pathway is important in mediating a wide range of biological activities, including embryological development, wound healing, tissue regeneration, angiogenesis, proliferation, survival, scattering, motility, invasion and morphogenic differentiation. HGF and/or c-Met are expressed at abnormally high levels in a large variety of solid tumors. Various c-Met mutations have been described in many solid tumors and some hematologic malignancies. Therefore, inhibition of the HGF/c-Met signaling pathway has great potential in molecular targeted cancer therapy. Many patent applications associated with inhibition of the HGF/c-Met axis have been published in the past few years. There are four small molecule c-Met inhibitors presently in clinical trials. This review focusses on recent patent applications for small molecule c-Met inhibitors and their potential applications in cancer therapy.

Keywords::

• c-Met
• hepatocyte growth factor
• hepatocyte growth factor receptor
• metastasis
• proliferation
• receptor tyrosine kinase
• scatter factor
• vascular endothelial growth factor receptor