FMS Kinase Inhibitors: Current Status and Future Prospects

Med Res Rev. 2013 May;33(3):599-636. doi: 10.1002/med.21258. Epub 2012 Mar 20.

Abstract

FMS, first discovered as the oncogene responsible for Feline McDonough Sarcoma, is a type III receptor tyrosine kinase that binds to the macrophage or monocyte colony-stimulating factor (M-CSF or CSF-1). Signal transduction through that binding results in survival, proliferation, and differentiation of monocyte/macrophage lineage. Overexpression of CSF-1 and/or FMS has been implicated in a number of disease states such as the growth of metastasis of certain types of cancer, in promoting osteoclast proliferation in bone osteolysis, and many inflammatory disorders. Inhibition of CSF-1 and/or FMS may help treat these pathological conditions. This article reviews FMS gene, FMS kinase, CSF-1, IL-34, and their roles in bone osteolysis, cancer biology, and inflammation. Monoclonal antibodies, FMS crystal structure, and small molecule FMS kinase inhibitors of different chemical scaffolds are also reviewed.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / therapeutic use
  • Crystallization
  • Genes, fms / physiology
  • Humans
  • Inflammation / physiopathology
  • Interleukins / physiology
  • Macrophage Colony-Stimulating Factor / immunology
  • Macrophage Colony-Stimulating Factor / physiology
  • Neoplasms / physiopathology
  • Osteolysis / physiopathology
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / classification
  • Receptor, Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Receptor, Macrophage Colony-Stimulating Factor / genetics
  • Receptor, Macrophage Colony-Stimulating Factor / immunology
  • Receptor, Macrophage Colony-Stimulating Factor / physiology

Substances

  • Antibodies, Monoclonal
  • IL34 protein, human
  • Interleukins
  • Protein Kinase Inhibitors
  • Macrophage Colony-Stimulating Factor
  • Receptor, Macrophage Colony-Stimulating Factor