COT (Tpl2 in mice) is a serine/threonine MAP3 kinase that regulates production 
of TNF-alpha and other pro-inflammatory cytokines such as IL-1beta via the 
ERK/MAP kinase pathway. As TNF-alpha and IL-1beta 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.