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Chemical Compound Review

CHEMBL96741     4-[3-(cyclopropylmethyl)-5- (4...

Synonyms: AG-J-92190, SureCN4915662, CTK7C0283, DNC007141, SB-216995, ...
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Disease relevance of SB6

  • Pyridinylimidazole compounds are specific inhibitors of p38 MAP kinase that block the production of the cytokines interleukin-1beta and tumor necrosis factor alpha, and they are effective in animal models of arthritis, bone resorption and endotoxin shock [1].

High impact information on SB6


Biological context of SB6

  • Mutagenesis showed that a single residue difference between p38 MAP kinase and other MAP kinases is sufficient to confer selectivity among pyridinylimidazole compounds [1].

Anatomical context of SB6

  • Recently we reported that the pyridinylimidazole class of p38 mitogen-activated protein (MAP) kinase inhibitors potently inhibited the facilitated transport of nucleosides and nucleoside analogs in K562 cells [6].

Associations of SB6 with other chemical compounds

  • The anti-inflammatory agent pyridinylimidazole and its analogs (SB [SmithKline Beecham] compounds) are highly potent and selective inhibitors of p38, but not of the closely-related ERK2, or other serine/threonine kinases [7].

Gene context of SB6

  • Pyridinylimidazole 11 potently inhibited LPS-induced TNFalpha in mice, showed good efficacy in the established rat adjuvant (ED(50): 10 mg/kg po b.i.d.) and collagen induced arthritis (ED(50): 5 mg/kg po b.i.d.) with disease modifying properties based on histological analysis of the joints [8].


  1. The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase. Wilson, K.P., McCaffrey, P.G., Hsiao, K., Pazhanisamy, S., Galullo, V., Bemis, G.W., Fitzgibbon, M.J., Caron, P.R., Murcko, M.A., Su, M.S. Chem. Biol. (1997) [Pubmed]
  2. Regulation of interleukin-1beta -induced platelet-derived growth factor receptor-alpha expression in rat pulmonary myofibroblasts by p38 mitogen-activated protein kinase. Wang, Y.Z., Zhang, P., Rice, A.B., Bonner, J.C. J. Biol. Chem. (2000) [Pubmed]
  3. Regulation of interleukin-1beta-induced interleukin-6 gene expression in human fibroblast-like synoviocytes by p38 mitogen-activated protein kinase. Miyazawa, K., Mori, A., Miyata, H., Akahane, M., Ajisawa, Y., Okudaira, H. J. Biol. Chem. (1998) [Pubmed]
  4. Regulation of urokinase plasminogen activator by epigallocatechin-3-gallate in human fibrosarcoma cells. Kim, M.H., Jung, M.A., Hwang, Y.S., Jeong, M., Kim, S.M., Ahn, S.J., Shin, B.A., Ahn, B.W., Jung, Y.D. Eur. J. Pharmacol. (2004) [Pubmed]
  5. Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase. Stelmach, J.E., Liu, L., Patel, S.B., Pivnichny, J.V., Scapin, G., Singh, S., Hop, C.E., Wang, Z., Strauss, J.R., Cameron, P.M., Nichols, E.A., O'Keefe, S.J., O'Neill, E.A., Schmatz, D.M., Schwartz, C.D., Thompson, C.M., Zaller, D.M., Doherty, J.B. Bioorg. Med. Chem. Lett. (2003) [Pubmed]
  6. Inhibition of nucleoside transport by protein kinase inhibitors. Huang, M., Wang, Y., Cogut, S.B., Mitchell, B.S., Graves, L.M. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  7. Structural basis of inhibitor selectivity in MAP kinases. Wang, Z., Canagarajah, B.J., Boehm, J.C., Kassisà, S., Cobb, M.H., Young, P.R., Abdel-Meguid, S., Adams, J.L., Goldsmith, E.J. Structure (1998) [Pubmed]
  8. SAR of 2,6-diamino-3,5-difluoropyridinyl substituted heterocycles as novel p38MAP kinase inhibitors. Revesz, L., Di Padova, F.E., Buhl, T., Feifel, R., Gram, H., Hiestand, P., Manning, U., Wolf, R., Zimmerlin, A.G. Bioorg. Med. Chem. Lett. (2002) [Pubmed]
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