TAK1 inhibition in the DFG-out conformation

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, Lyn H. Jones (Lead / Corresponding author)

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12 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)500-505
Number of pages6
JournalChemical Biology and Drug Design
Volume82
Issue number5
Early online date16 Oct 2013
DOIs
Publication statusPublished - 1 Nov 2013

Keywords

  • Chemical biology
  • Drug design
  • Kinase
  • Phosphatase
  • Structure-based drug design
  • X-ray crystallography

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    Kilty, I., Green, M. P., Bell, A. S., Brown, D. G., Dodd, P. G., Hewson, C., Hughes, S. J., Phillips, C., Ryckmans, T., Smith, R. T., van Hoorn, W. P., Cohen, P., & Jones, L. H. (2013). TAK1 inhibition in the DFG-out conformation. Chemical Biology and Drug Design, 82(5), 500-505. https://doi.org/10.1111/cbdd.12169