TAK1 Inhibition in the DFG-Out Conformation

Abstract The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.