| Message: | What is GW0742？
GW0742 is a small molecule agonist of human peroxisome proliferator-activated receptor delta (PPARdelta). It shows an EC50 of 1.1 nM against PPARδ, 100-fold selectivity over other human subtypes.
Benefit:The effects of a high-affinity PPAR-β/δ agonist, GW0742, in a mouse model of carrageenan (CAR)-induced pleurisy. Injection of CAR into the pleural cavity of mice elicited an acute inflammatory response characterized by accumulation of fluid containing a large number of neutrophils (polymorphonuclear leukocytes) in the pleural cavity, infiltration of polymorphonuclear leukocytes in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, TNF-α, and IL-1β. Furthermore, CAR induced lung apoptosis (Bax and Bcl-2 expression), and nitrotyrosine formation was determined by immunohistochemical analysis of lung tissues. Administration of GW0742 (0.3 mg/kg, i.p. bolus) 30 min before and 30 min after a challenge with CAR caused a reduction in all the parameters of inflammation measured. Thus, based on these findings, we propose that a PPAR-β/δ agonist such as GW0742 may be useful in the treatment of various inflammatory diseases.
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