de Leval X, Delarge J, Devel P, Neven P, Michaux C, Masereel B, Pirotte B, David J L, Henrotin Y, Dogne J M
Department of Medicinal Chemistry, University of Liège, Liège, B-4000, Belgium.
Prostaglandins Leukot Essent Fatty Acids. 2001 Apr-May;64(4-5):211-6. doi: 10.1054/plef.2001.0262.
Cyclooxygenase is the key enzyme in the biosynthesis of prostanoids, biologically active substances involved in several physiological processes and also in pathological conditions such as inflammation. It has been well known for 10 years that this enzyme exists under two forms: a constitutive (COX-1) and an inducible form (COX-2). Both enzymes are sensitive to inhibition by conventional non-steroidal anti-inflammatory drugs (NSAIDs). Observations were made that COX-1 was mainly involved in homeostatic processes, while the COX-2 expression was associated with pathological conditions leading to the development of COX-2 selective inhibitors. Several methods have been reported for the evaluation of the COX-1 and COX-2 inhibitory potency and selectivity of conventional or COX-2 selective NSAIDs. In this study, we evaluated the COXs inhibitory profile of both conventional NSAIDs and COX-2 selective inhibitors using two different in vitro methods: the first test was performed using purified enzymes while the second method consisted of a whole blood assay. The results obtained with reference drugs in these two assays will be discussed and compared in this article.
环氧化酶是类花生酸生物合成中的关键酶，类花生酸是参与多种生理过程以及诸如炎症等病理状况的生物活性物质。十年来人们一直清楚地知道这种酶以两种形式存在：一种是组成型（COX - 1），另一种是诱导型（COX - 2）。这两种酶都对传统非甾体抗炎药（NSAIDs）的抑制作用敏感。有观察表明，COX - 1主要参与稳态过程，而COX - 2的表达与导致COX - 2选择性抑制剂研发的病理状况相关。已经报道了几种评估传统或COX - 2选择性NSAIDs对COX - 1和COX - 2抑制效力及选择性的方法。在本研究中，我们使用两种不同的体外方法评估了传统NSAIDs和COX - 2选择性抑制剂对COXs的抑制特征：第一种试验使用纯化酶进行，而第二种方法是全血检测。本文将讨论并比较在这两种检测中使用参考药物所获得的结果。
