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 sitedirected 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.

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

CAVALLI, ANDREA;
2013

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 sitedirected 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.
Laura Bertolacci;Elisa Romeo;Marina Veronesi;Paola Magotti;Clara Albani;Mauro Dionisi;Chiara Lambruschini;Rita Scarpelli;Andrea Cavalli;Marco De Vivo;Daniele Piomelli;Gianpiero Garau
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/145516
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