title: Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids.
abstract: The endocannabinoid system, most popularly known as the target of the psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), is a signaling network that modulates a diverse range of physiological processes including nociception, behavior, cognitive function, appetite, metabolism, motor control, memory formation, and inflammation. While THC and its derivatives have garnered notoriety in the eyes of the public, the endocannabinoid system consists of two endogenous signaling lipids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide), which activate cannabinoid receptors CB1 and CB2 in the nervous system and peripheral tissues. This review will focus on the recent efforts to chemically manipulate 2-AG signaling through the development of inhibitors of the 2-AG-synthesizing enzyme diacylglycerol lipase (DAGL) or the 2-AG-degrading enzyme monoacylglycerol lipase (MAGL), and assessing the therapeutic potential of DAGL and MAGL inhibitors in pain, inflammation, degenerative diseases, tissue injury, and cancer.
authors.affiliation: Program in Metabolic Biology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA. dnomura@berkeley.edu.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Kohnz
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Nomura
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism*; D013759:Dronabinol / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015777:Eicosanoids / Q000378:metabolism*; D063388:Endocannabinoids / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D005989:Glycerides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019964:Mood Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001095:Arachidonic Acids; D015777:Eicosanoids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D013759:Dronabinol; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases; D008071:Lipoprotein Lipase