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Cot/Tpl-2 Protein Kinase as a Target for the Treatment of Inflammatory Disease

[ Vol. 9 , Issue. 7 ]

Author(s):

D. George and A. Salmeron   Pages 611 - 622 ( 12 )

Abstract:


Cot/Tpl-2/MAP3K8 is a serine/threonine protein kinase that is essential for lipopolysaccharide (LPS)-induced activation of the MEK/ERK pathway in macrophages as demonstrated in Cot/Tpl-2-deficient mice. Cot/Tpl-2 kinase activation plays an integral role in the production of pro-inflammatory cytokines such as TNF and IL-1β in this immune cell type. Elevated levels of these cytokines have been clinically implicated as mediators of a number of autoimmune diseases, in particular, the pain and joint destruction of rheumatoid arthritis. By inference, pharmaceutical agents that inhibit Cot/Tpl-2 kinase have the potential to be novel and effective therapies for the treatment of these diseases. This review will describe the physiological regulation and importance of Cot/Tpl-2 in inflammation as well as the landscape of small molecules that have been reported as Cot/Tpl-2 inhibitors.

Keywords:

Cot/Tpl-2, serine/threonine kinase, LPS, macrophages, kinase inhibitors

Affiliation:

Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA.



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