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

作者：Spahiu Linda; Stenberg Patric; Larsson Charlotte; Wannberg Johan; Alterman Mathias; Kull Bjorn; Nekhotiaeva Natalia; Morgenstern Ralf^*

来源：Assay and Drug Development Technologies, 2011, 9(5): 487-495.

DOI：10.1089/adt.2010.0350

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 IC(50) 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.

• 出版日期2011-10