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 / 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. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 135:(2013), pp. 22-25. [10.1021/ja308733u]
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
