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Pyridinylimidazoles, often termed CSAIDs, are a class of anti-inflammatory compounds that inhibit eicosanoid production and suppress the synthesis of cytokines in human monocytes.1 Because of its high specificity, one predominant pyridinylimidazole, SB203580, is frequently used to inhibit p38 MAPK, the tyrosine kinase activated by environmental stresses and inflammatory cytokines.2 CAY10571 is an analog of SB203580. It inhibits IL-1 production in the human monocytic cell line THP with an IC50 value of 0.20 µM and binds CSAID binding protein, a serine/threonine kinase homologous to p38, inhibiting its kinase activity with an IC50 value of 0.03 µM.3,4 CAY105571 also inhibits 5-lipoxygenase production in RBL-1 cells with an IC50 value of 24 µM.3
1
Lee, J.C., Laydon, J.T., McDonnell, P.C., et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature372(22)739-746(1994).
2
Cuenda, A., Rouse, J., Doza, Y.N., et al. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett364229-233(1995).
3
Gallagher, T.F., Fier-Thompson, S.M., Garigipati, R.S., et al. 2,4,5-triarylimidazole inhibitors of IL-1 biosynthesis. Bioorg Med Chem Lett5(11)1171-1176(1995).
4
Gallagher, T.F., Seibel, G.L., Kassis, S., et al. Regulation of stress-induced cytokine production by pyridinylimidazoles; Inhibition of CSBP kinase. Bioorg Med Chem5(1)49-64(1997).
Gallagher, T.F., Seibel, G.L., Kassis, S., et al. Regulation of stress-induced cytokine production by pyridinylimidazoles; Inhibition of CSBP kinase. Bioorg Med Chem5(1)49-64(1997).
Gallagher, T.F., Fier-Thompson, S.M., Garigipati, R.S., et al. 2,4,5-triarylimidazole inhibitors of IL-1 biosynthesis. Bioorg Med Chem Lett5(11)1171-1176(1995).
Lee, J.C., Laydon, J.T., McDonnell, P.C., et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature372(22)739-746(1994).
Cuenda, A., Rouse, J., Doza, Y.N., et al. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett364229-233(1995).