TAK1 Inhibition in the DFG-Out Conformation (pages 500–505)
Iain Kilty, Martin P. Green, Andrew S. Bell, David G. Brown, Peter G. Dodd, Christopher Hewson, Samantha J. Hughes, Christopher Phillips, Thomas Ryckmans, Robert T. Smith, Willem P. van Hoorn, Philip Cohen and Lyn H. Jones
Article first published online: 16 OCT 2013 | DOI: 10.1111/cbdd.12169
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.