title: A binding site for nonsteroidal anti-inflammatory drugs in fatty acid amide hydrolase.
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.
authors.affiliation: Drug Discovery and Development, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bertolacci
authors.forename: Elisa
authors.initials: E
authors.lastname: Romeo
authors.forename: Marina
authors.initials: M
authors.lastname: Veronesi
authors.forename: Paola
authors.initials: P
authors.lastname: Magotti
authors.forename: Clara
authors.initials: C
authors.lastname: Albani
authors.forename: Mauro
authors.initials: M
authors.lastname: Dionisi
authors.forename: Chiara
authors.initials: C
authors.lastname: Lambruschini
authors.forename: Rita
authors.initials: R
authors.lastname: Scarpelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Marco
authors.initials: M
authors.lastname: De Vivo
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Garau
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D000099252:Fatty Acid Amide Hydrolases; C007005:carprofen