A Binding Site for Nonsteroidal Anti-inflammatory Drugs in Fatty Acid Amide Hydrolase

被引：53

作者：

Bertolacci, Laura ^{[1
]}

Romeo, Elisa ^{[1
]}

Veronesi, Marina ^{[1
]}

Magotti, Paola ^{[1
]}

Albani, Clara ^{[1
]}

Dionisi, Mauro ^{[1
]}

Lambruschini, Chiara ^{[1
]}

Scarpelli, Rita ^{[1
]}

Cavalli, Andrea ^{[2
]}

De Vivo, Marco ^{[1
]}

Piomelli, Daniele ^{[1
,3
]}

Garau, Gianpiero ^{[1
]}

机构：

[1] Ist Italiano Tecnol, I-16163 Genoa, Italy

[2] Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy

[3] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2013年 / 135卷 / 01期

关键词：

ALPHA-KETOHETEROCYCLE INHIBITORS; SELECTIVE FAAH INHIBITOR; PAIN INITIATION; CYCLOOXYGENASE; ENZYME; INDOMETHACIN; DISCOVERY; ENDOCANNABINOIDS; PROSTAGLANDINS; INFLAMMATION;

D O I：

10.1021/ja308733u

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

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收藏

页码：22 / 25

页数：4

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