A Facilitated Approach to Evaluate the Inhibitor Mode and Potency of Compounds Targeting Microsomal Prostaglandin E Synthase-1

Microsomal prostaglandin E-2 synthase-1 (MPGES1) catalyzes the formation of prostaglandin E-2 from the endoperoxide prostaglandin H-2. MPGES1 expression is induced in inflammatory diseases, and this enzyme is regarded as a potential drug target. To aid in the drug discovery effort, a simple method for determination of inhibition mechanism and potency toward both prostaglandin H-2 and glutathione (GSH) has been developed. Using an assay with thiobarbituric acid-based detection, the inhibitory effects of six MPGES1 inhibitors were evaluated. The IC50 values obtained at three substrate (S) concentrations ([S] < K-M, [S] approximate to K-M, [S] > K-M) were used to estimate inhibition modality and inhibition constant values. This facilitated strategy is a useful and general screening method to evaluate the inhibitory effects of new drug compounds.