Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase

  • Bioorg Med Chem. 1997 Jan;5(1):49-64. doi: 10.1016/s0968-0896(96)00212-x.
T F Gallagher  1 ,  G L Seibel ,  S Kassis ,  J T Laydon ,  M J Blumenthal ,  J C Lee ,  D Lee ,  J C Boehm ,  S M Fier-Thompson ,  J W Abt ,  M E Soreson ,  J M Smietana ,  R F Hall ,  R S Garigipati ,  P E Bender ,  K F Erhard ,  A J Krog ,  G A Hofmann ,  P L Sheldrake ,  P C McDonnell ,  S Kumar ,  P R Young ,  J L Adams
Affiliations
  • 1. Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
PMID: 9043657 DOI: 10.1016/s0968-0896(96)00212-x
Abstract

Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKC Alpha and ERK kinase activity is observed.

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