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Identification of a selective thieno[2,3-c]pyridine inhibitor of COT kinase and TNF-alpha production.

Cusack K, Allen H, Bischoff A, Clabbers A, Dixon R, Fix-Stenzel S, Friedman M, Gaumont Y, George D, Gordon T, Grongsaard P, Janssen B, Jia Y, Moskey M, Quinn C, Salmeron A, Thomas C, Wallace G, Wishart N, Yu Z.

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1722-5. doi: 10.1016/j.bmcl.2009.01.088. Epub 2009 Jan 30.


Inhibitors of tumor progression loci-2 (Tpl2) kinase and tumor necrosis factor alpha (TNF-alpha) production: selectivity and in vivo antiinflammatory activity of novel 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles.

Green N, Hu Y, Janz K, Li HQ, Kaila N, Guler S, Thomason J, Joseph-McCarthy D, Tam SY, Hotchandani R, Wu J, Huang A, Wang Q, Leung L, Pelker J, Marusic S, Hsu S, Telliez JB, Hall JP, Cuozzo JW, Lin LL.

J Med Chem. 2007 Sep 20;50(19):4728-45. Epub 2007 Aug 23.


Luteolin, a novel natural inhibitor of tumor progression locus 2 serine/threonine kinase, inhibits tumor necrosis factor-alpha-induced cyclooxygenase-2 expression in JB6 mouse epidermis cells.

Kim JE, Son JE, Jang YJ, Lee DE, Kang NJ, Jung SK, Heo YS, Lee KW, Lee HJ.

J Pharmacol Exp Ther. 2011 Sep;338(3):1013-22. doi: 10.1124/jpet.111.179200. Epub 2011 Jun 24.


Cot/Tpl-2 protein kinase as a target for the treatment of inflammatory disease.

George D, Salmeron A.

Curr Top Med Chem. 2009;9(7):611-22. Review.


Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood.

Hall JP, Kurdi Y, Hsu S, Cuozzo J, Liu J, Telliez JB, Seidl KJ, Winkler A, Hu Y, Green N, Askew GR, Tam S, Clark JD, Lin LL.

J Biol Chem. 2007 Nov 16;282(46):33295-304. Epub 2007 Sep 11.


Serine/threonine kinase, Cot/Tpl2, regulates renal cell apoptosis in ischaemia/reperfusion injury.

Yaomura T, Tsuboi N, Urahama Y, Hobo A, Sugimoto K, Miyoshi J, Matsuguchi T, Reiji K, Matsuo S, Yuzawa Y.

Nephrology (Carlton). 2008 Oct;13(5):397-404. doi: 10.1111/j.1440-1797.2008.00959.x. Epub 2008 May 29.


Phosphorylation of threonine 290 in the activation loop of Tpl2/Cot is necessary but not sufficient for kinase activity.

Luciano BS, Hsu S, Channavajhala PL, Lin LL, Cuozzo JW.

J Biol Chem. 2004 Dec 10;279(50):52117-23. Epub 2004 Oct 4.


Discovery of thieno[2,3-c]pyridines as potent COT inhibitors.

George D, Friedman M, Allen H, Argiriadi M, Barberis C, Bischoff A, Clabbers A, Cusack K, Dixon R, Fix-Stenzel S, Gordon T, Janssen B, Jia Y, Moskey M, Quinn C, Salmeron JA, Wishart N, Woller K, Yu Z.

Bioorg Med Chem Lett. 2008 Sep 15;18(18):4952-5. doi: 10.1016/j.bmcl.2008.08.037. Epub 2008 Aug 14.


A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL-12 production and Th cell differentiation.

Sugimoto K, Ohata M, Miyoshi J, Ishizaki H, Tsuboi N, Masuda A, Yoshikai Y, Takamoto M, Sugane K, Matsuo S, Shimada Y, Matsuguchi T.

J Clin Invest. 2004 Sep;114(6):857-66.


Cot/Tpl2 regulates IL-23 p19 expression in LPS-stimulated macrophages through ERK activation.

Kakimoto K, Musikacharoen T, Chiba N, Bandow K, Ohnishi T, Matsuguchi T.

J Physiol Biochem. 2010 Mar;66(1):47-53. doi: 10.1007/s13105-010-0007-9. Epub 2010 Apr 20.


Interleukin-1alpha stimulates proinflammatory cytokine expression in human cardiac myofibroblasts.

Turner NA, Das A, Warburton P, O'Regan DJ, Ball SG, Porter KE.

Am J Physiol Heart Circ Physiol. 2009 Sep;297(3):H1117-27. doi: 10.1152/ajpheart.00372.2009. Epub 2009 Jul 31.


Inhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles: synthesis and structure-activity relationships.

Gavrin LK, Green N, Hu Y, Janz K, Kaila N, Li HQ, Tam SY, Thomason JR, Gopalsamy A, Ciszewski G, Cuozzo JW, Hall JP, Hsu S, Telliez JB, Lin LL.

Bioorg Med Chem Lett. 2005 Dec 1;15(23):5288-92. Epub 2005 Sep 13.


Functional roles of Cot/Tpl2 in mast cell responses to lipopolysaccharide and FcεRI-clustering.

Chiba N, Kakimoto K, Masuda A, Matsuguchi T.

Biochem Biophys Res Commun. 2010 Nov 5;402(1):1-6. doi: 10.1016/j.bbrc.2010.08.075. Epub 2010 Aug 21.


Flavonol-rich RVHxR from Rhus verniciflua Stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models.

Lee JD, Huh JE, Jeon G, Yang HR, Woo HS, Choi DY, Park DS.

Int Immunopharmacol. 2009 Mar;9(3):268-76. doi: 10.1016/j.intimp.2008.11.005. Epub 2008 Dec 25.


Central role of the MEK/ERK MAP kinase pathway in a mouse model of rheumatoid arthritis: potential proinflammatory mechanisms.

Thiel MJ, Schaefer CJ, Lesch ME, Mobley JL, Dudley DT, Tecle H, Barrett SD, Schrier DJ, Flory CM.

Arthritis Rheum. 2007 Oct;56(10):3347-57.

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