CHAPTER 7:Syk Kinase Inhibitors

Diseases such as rheumatoid arthritis, asthma and chronic allergies are thought to be the result of chronic inflammatory processes and are the subject of intense research by academia and pharmaceutical companies. One of the major proteins targeted by this research is Syk kinase. Since Syk is uniquely positioned at the origins of multiple inflammatory pathways in many cell types, inhibition of the activity of this kinase promises to slow the debilitating effects of chronic inflammation. This review will present a discussion of what has been learned through the efforts on this field of research and report on the recent progress toward clinical drug development. Initially, the biologic role of Syk in generating inflammation will be considered and some of the major genetic and animal studies that have been performed to validate Syk as a target will be described. In the second section, the structural features of the enzyme and approaches taken for the design of inhibitors will be presented. The third section will review the inhibitors that have been designed and chemotypes that have proved effective at inhibiting Syk. And finally, the results of clinical trials are described.