FMS Kinase Inhibitors: Current Status and Future Prospects

• Published in: Medicinal research reviews Vol. 33; no. 3; pp. 599 - 636
• Main Authors: El-Gamal, Mohammed I., Anbar, Hanan S., Yoo, Kyung Ho, Oh, Chang-Hyun
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.05.2013; Wiley Subscription Services, Inc
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - therapeutic use; Crystallization; CSF-1; CSF-1R; FMS; FMS kinase inhibitors; Genes, fms - physiology; Humans; IL-34; Inflammation - physiopathology; Interleukins - physiology; Macrophage Colony-Stimulating Factor - immunology; Macrophage Colony-Stimulating Factor - physiology; monoclonal antibodies; Neoplasms - physiopathology; Osteolysis - physiopathology; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - classification; Proteins; 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
• ISSN: 0198-6325; 1098-1128
• DOI: 10.1002/med.21258

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.