A novel fluorophosphonate inhibitor of the biosynthesis of the endocannabinoid 2‐arachidonoylglycerol with potential anti‐obesity effects

• Published in: British journal of pharmacology Vol. 169; no. 4; pp. 784 - 793
• Main Authors: Bisogno, Tiziana, Mahadevan, Anu, Coccurello, Roberto, Chang, Jae Won, Allarà, Marco, Chen, Yugang, Giacovazzo, Giacomo, Lichtman, Aron, Cravatt, Benjamin, Moles, Anna, Di Marzo, Vincenzo
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2013
• Subjects: 2‐arachidonoylglycerol; Animals; Anti-Obesity Agents - administration & dosage; Anti-Obesity Agents - pharmacology; Anti-Obesity Agents - therapeutic use; anti‐obesity effects; Arachidonic Acids - antagonists & inhibitors; Arachidonic Acids - metabolism; Behavior, Animal - drug effects; Biosynthesis; cannabinoid; Cell Line; Cercopithecus aethiops; diacylglycerol; Dose-Response Relationship, Drug; Endocannabinoids - antagonists & inhibitors; Endocannabinoids - metabolism; Energy Intake - drug effects; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Glycerides - antagonists & inhibitors; Glycerides - metabolism; Glycerophospholipids - administration & dosage; Glycerophospholipids - pharmacology; Glycerophospholipids - therapeutic use; Humans; Hypothalamus - drug effects; Hypothalamus - enzymology; Hypothalamus - metabolism; inhibitor; Lipoprotein Lipase - antagonists & inhibitors; Lipoprotein Lipase - genetics; Lipoprotein Lipase - metabolism; Liver - drug effects; Liver - enzymology; Liver - metabolism; Male; Medical research; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons - drug effects; Neurons - enzymology; Neurons - metabolism; Obesity; Obesity - drug therapy; Obesity - enzymology; Obesity - metabolism; Oleic Acids - administration & dosage; Oleic Acids - pharmacology; Oleic Acids - therapeutic use; Organophosphonates - administration & dosage; Organophosphonates - pharmacology; Organophosphonates - therapeutic use; Rats; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Rodents; serine lipase; Sterol Esterase - antagonists & inhibitors; Sterol Esterase - metabolism; Themed Section: Cannabinoids 2012, Part Two

Background and Purpose The development of potent and selective inhibitors of the biosynthesis of the endocannabinoid 2‐arachidonoylglycerol (2‐AG) via DAG lipases (DAGL) α and β is just starting to be considered as a novel and promising source of pharmaceuticals for the treatment of disorders that m...