脂肪酸酰胺水解酶的非甾体抗炎药物结合位点。
A binding site for nonsteroidal anti-inflammatory drugs in fatty acid amide hydrolase.
机构信息
Drug Discovery and Development, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
出版信息
J Am Chem Soc. 2013 Jan 9;135(1):22-5. doi: 10.1021/ja308733u. Epub 2012 Dec 21.
Abstract
In addition to inhibiting the cyclooxygenase (COX)-mediated biosynthesis of prostanoids, various widely used nonsteroidal anti-inflammatory drugs (NSAIDs) enhance endocannabinoid signaling by blocking the anandamide-degrading membrane enzyme fatty acid amide hydrolase (FAAH). The X-ray structure of FAAH in complex with the NSAID carprofen, along with site-directed mutagenesis, enzyme activity assays, and NMR analysis, has revealed the molecular details of this interaction, providing information that may guide the design of dual FAAH-COX inhibitors with superior analgesic efficacy.
摘要
除了抑制环氧化酶（COX）介导的前列腺素生物合成外，各种广泛使用的非甾体抗炎药（NSAIDs）还通过阻断大麻素降解膜酶脂肪酸酰胺水解酶（FAAH）来增强内源性大麻素信号。FAAH 与 NSAID 卡洛芬形成复合物的 X 射线结构，以及定点突变、酶活性测定和 NMR 分析，揭示了这种相互作用的分子细节，为设计具有优异镇痛效果的双重 FAAH-COX 抑制剂提供了信息。
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