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Cyclooxygenase-2 Inhibitor SC-236 [4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] Benzenesulfonamide] Suppresses Nuclear factor-kappaB Activation and Phosphorylation of p38 Mitogen-Activated Protein Kinase, Extracellular Signal-Regulated Kinase, and c-Jun N-terminal Kinase in Human Mast Cell Line Cells

Cyclooxygenase-2 Inhibitor SC-236 [4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] Benzenesulfonamide] Suppresses Nuclear factor-kappaB Activation and Phosphorylation of p38 Mitogen-Activated Protein Kinase, Extracellular Signal-Regulated Kinase, and c-Jun N-terminal Kinase in Human Mast Cell Line Cells

Su-Jin Kim, Hyun-Ja Jeong, In-Young Choi, Kang-Min Lee, Rae-Kil Park, Seung-Heon Hong, Hyung-Min Kim

J Pharmacol Exp Ther. 2005 Jul;314(1):27-34.

PMID: 15784648

Abstract:

SC-236 [4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] benzenesulfonamide; C16H11ClF3N3O2S] is a highly selective cyclooxygenase (COX)-2 inhibitor. However, the exact mechanism that accounts for the anti-inflammatory effect of SC-236 is not completely understood. The aim of the present study was to elucidate whether and how SC-236 modulates the inflammatory reaction in a stimulated human mast cell (HMC) line, HMC-1. SC-236 inhibited the expression of tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, vascular endothelial growth factor, COX-2, inducible nitric-oxide synthase, and hypoxia-inducible factor-1alpha in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated HMC-1. SC-236 suppressed nuclear factor (NF)-kappaB activation induced by PMACI, leading to suppression of IkappaB-alpha phosphorylation and degradation. SC-236 also suppressed strong induction of NF-kappaB promoter-mediated luciferase activity. In addition, SC-236 suppressed PMACI-induced phosphorylation of the mitogen-activated protein kinase p38, the extracellular-regulated kinase p44, and the c-Jun N-terminal kinase and induced expression of mitogen-activated protein kinase phosphatase-1. These results provide new insight into the pharmacological actions of SC-236 as a potential molecule for therapy of mast cell-mediated inflammatory diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP170569865	SC-236		170569-86-5	Price

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