CC 05, a novel anti-inflammatory compound, exerts its effect by inhibition of cyclooxygenase-2 activity

In the present study, we examined the anti-inflammation of a novel compound, 4-[5-(3-amino-4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (CC 05) in vitro and in vivo. In an in vitro cell-based assay, CC 05 inhibited cyclooxygenase (COX)-2-derived prostaglandin E(2) (PGE(2)) synthesis with an IC(50) value of 0.328+/-0.04 microM compared with an IC(50) value of 14.34+/-0.05 microM for the inhibition of COX-1-derived PGE(2) synthesis. In two in vivo rodent models, CC 05 (12.5, 25 and 50 mg/kg, i.g.) is a moderate potential and selective inhibitor of COX-2. It can reduce carrageenan-induced paw edema and PGE(2) production in the inflamed pouch dose-dependently without affecting the PGE(2) production in stomachs. Furthermore, CC 05 had no effect on COX-2 mRNA and protein expression in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 human macrophages stimulated with lipopolysaccharide (LPS). These results demonstrate that CC 05 is a novel COX-2 inhibitor and the anti-inflammatory action is not directed towards the transcription or translation of the COX-2 gene but only to the enzymatic activity of the protein.