Walker Mark C, Gierse James K
Pfizer Global Research and Development, Chesterfield, MO, USA.
Methods Mol Biol. 2010;644:131-44. doi: 10.1007/978-1-59745-364-6_11.
Cyclooxygenases (COX), or Prostaglandin H Synthases (PGHS), are the target enzymes for nonsteroidal anti-inflammatory drugs (NSAIDS). The identification of two isoforms of COX nearly 20 years ago stimulated a flurry of research activity to identify novel, selective inhibitors that could provide potential benefit over existing nonselective NSAIDS. An important contribution to this discovery effort was the development of various in vitro and in vivo assays to support rapid screening of chemical libraries, characterization of inhibitory mechanism, and determination of potency and efficacy to guide follow-up medicinal chemistry efforts. Several assay methods for the in vitro evaluation of COX activity and mechanism of inhibition by test compounds will be reviewed. Each of these methods has inherent advantages and disadvantages with regard to application and the mechanistic detail provided.
环氧化酶（COX），即前列腺素H合成酶（PGHS），是非甾体抗炎药（NSAIDs）的靶标酶。近20年前两种COX同工型的鉴定激发了一系列研究活动，以寻找新型的选择性抑制剂，这些抑制剂可能比现有的非选择性NSAIDs更具潜在优势。对这一发现工作的一项重要贡献是开发了各种体外和体内试验，以支持化学文库的快速筛选、抑制机制的表征以及效力和功效的测定，从而指导后续的药物化学研究。本文将综述几种用于体外评估COX活性以及测试化合物抑制机制的试验方法。就应用和所提供的机制细节而言，这些方法中的每一种都有其固有的优点和缺点。
