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

被引：7

作者：

Spahiu, Linda ^{[3
]}

Stenberg, Patric ^{[2
,3
]}

Larsson, Charlotte ^{[3
]}

Wannberg, Johan ^{[3
]}

Alterman, Mathias ^{[3
]}

Kull, Bjorn ^{[3
]}

Nekhotiaeva, Natalia ^{[3
]}

Morgenstern, Ralf ^{[1
,2
,3
]}

机构：

[1] Karolinska Inst, Inst Environm Med, SE-17177 Stockholm, Sweden

[2] NovaSAID AB, Solna, Sweden

[3] Actar AB, Solna, Sweden

来源：

ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES | 2011年 / 9卷 / 05期

基金：

瑞典研究理事会;

关键词：

E-2; SYNTHASE; STRUCTURAL BASIS; FUNCTIONAL-CHARACTERIZATION; COLORECTAL-CANCER; CRYSTAL-STRUCTURE; PROGRESS CURVES; BIOSYNTHESIS; CYCLOOXYGENASE-2; IDENTIFICATION; PURIFICATION;

D O I：

10.1089/adt.2010.0350

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：487 / 495

页数：9

共 44 条

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