The COX-2 inhibitor SC-236 exerts anti-inflammatory effects by suppressing phosphorylation of ERK in a murine model.

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Kim SJ, Jeong HJ, Moon PD, Myung NY, Kim MC, Kang TH, Lee KM, Park RK, So HS, Kim EC, An NH, Um JY, Kim HM, Hong SH

The COX-2 inhibitor SC-236 exerts anti-inflammatory effects by suppressing phosphorylation of ERK in a murine model.

Life Sci. 2007 Aug 23;81(11):863-72. doi: 10.1016/j.lfs.2007.06.027. Epub 2007 Sep 5.

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17822719 [ View in PubMed
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Abstract

SC-236, (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-]benzenesulfonamide; C(16)H(11)ClF(3)N(3)O(2)S) is a highly selective cyclooxygenase (COX)-2 inhibitor. Recently, there have been reports that SC-236 protects against cartilage damage in addition to reducing inflammation and pain for those with osteoarthritis. However, the mechanism involved in an inflammatory allergic reaction in a murine model has not been examined. The aim of the present study is to elucidate whether and how SC-236 modulates the inflammatory allergic reaction in a murine model. In this study, the anti-allergic effect was investigated using rat peritoneal mast cells, IgE-induced passive cutaneous anaphylaxis (PCA), and the ear-swelling model in mice. Also, we examined the inhibitory effect of SC-236 on the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. SC-236 was found to inhibit the ear-swelling response and histamine release in the murine model. Additionally, SC-236 was revealed to inhibit the PCA response and COX-2 expression. As a final step, the inhibitory mechanism of SC-236 was shown to occur through phosphorylation of extracellular signal-regulated protein kinase (ERK). These in vitro and in vivo results provide new insight into the pharmacological actions of SC-236 as a potential molecule for therapy for inflammatory allergic diseases.

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