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Soluble in DMSO or ethanol. The cytokine Tumor necrosis factor-alpha (TNF-alpha) is secreted by activated monocytes/macrophages and T lymphocytes and has been implicated in several disease states, including rheumatoid arthritis, inflammatory bowel disease, septic shock, and osteoporosis. Monocyte/macrophage production of TNF-alpha is dependent on the mitogen-activated protein kinase p38. The compound RWJ 67657 is a potent, orally active inhibitor of MAPK and it inhibited the release of TNF-alpha from LPA stimulated human mononuclear cells with an IC(50) of 3nM, as well as the release of TNF-alpha from peripheral blood mononuclear cells treated with the T cell stimulator and superantigen staphylococcal enterotoxin B with an IC(50) value of 13nM. Also RWJ 67657 was approximately 10-fold more potent than the literature standard p38 kinase inhibitor SB 203580 in all p38 dependent in vitro systems tested and is much more specific than SB 203580 for p38 kinaes. RWJ 67657 inhibited the enzymatic activity of recombinant p38alpha and beta, with in vitro IC(50) values of 1 and 11µM respectively, but not gamma or delta, and in further in vitro test across a panel of other enzymes RWJ 67657 demonstrated no other significant activity. Target: p38 , Kinase Group: CMGC , Substrate: Serine-Threonine
This website uses cookies, which are necessary for the technical operation of the website and are always set. Other cookies, which increase the usability of this website, serve for direct advertising or simplify interaction with other websites and social networks, will only be used with your consent.
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