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

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

Bioorganic & medicinal chemistry (1997-01-01)

T F Gallagher, 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

PMID9043657

摘要

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.