Identification of a selective thieno[2,3-c]pyridine inhibitor of COT kinase and TNF-α production

COT (Tpl2 in mice) is a serine/threonine MAP3 kinase that regulates production of TNF-α and other pro-inflammatory cytokines such as IL-1β via the ERK/MAP kinase pathway. As TNF-α and IL-1β are clinically validated targets for therapeutic intervention in rheumatoid arthritis (RA), blocking COT provides a potential avenue for amelioration of disease. Herein we describe identification of a cellular active selective small molecule inhibitor of COT kinase.

Graphical abstractCOT (Tpl2 in mice) is a serine/threonine MAP3 kinase that regulates production of TNF-α and other pro-inflammatory cytokines such as IL-1β via the ERK/MAP kinase pathway. As TNF-α and IL-1β are clinically validated targets for therapeutic intervention in rheumatoid arthritis (RA), blocking COT provides a potential avenue for amelioration of disease. Herein we describe identification of a cellular active selective small molecule inhibitor of COT kinase.Figure optionsDownload full-size imageDownload as PowerPoint slide