Cot/Tpl-2 protein kinase as a target for the treatment of inflammatory disease
D George, A Salmeron - Current topics in medicinal chemistry, 2009 - ingentaconnect.com
D George, A Salmeron
Current topics in medicinal chemistry, 2009•ingentaconnect.comCot/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 …
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 …
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.
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