Spahiu Linda, Stenberg Patric, Larsson Charlotte, Wannberg Johan, Alterman Mathias, Kull Björn, Nekhotiaeva Natalia, Morgenstern Ralf
Actar AB, Solna, Sweden.
Assay Drug Dev Technol. 2011 Oct;9(5):487-95. doi: 10.1089/adt.2010.0350. Epub 2011 May 11.
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]≈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.
微粒体前列腺素E(2)合成酶-1（MPGES1）催化内过氧化物前列腺素H(2)生成前列腺素E(2)。MPGES1的表达在炎症性疾病中被诱导，并且这种酶被视为一个潜在的药物靶点。为了辅助药物研发工作，已开发出一种简单的方法来确定对前列腺素H(2)和谷胱甘肽（GSH）的抑制机制及效力。使用基于硫代巴比妥酸检测的测定法，评估了六种MPGES1抑制剂的抑制作用。在三种底物（S）浓度（[S]<K(M)、[S]≈K(M)、[S]>K(M)）下获得的IC(50)值用于估计抑制模式和抑制常数。这种简便的策略是评估新药物化合物抑制作用的一种有用且通用的筛选方法。
