Abstract
Monoacylglycerol lipase (MAGL) is the major enzyme that catalyzes the hydrolysis of monoacylglycerols (MAGs). MAGL is responsible for degrading 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) and glycerol in the brain and specific tissues. The inhibition of MAGL could attenuate the inflammatory response. Here, we report a series of reversible non-covalent MAGL inhibitors via virtual screening combined with biochemical analysis. The hit, DC630-8 showed low-micromolar activity against MAGL in vitro, and exhibited significant anti-inflammatory effects.
Keywords:
Inflammation; Inhibitor; Monoacylglycerol lipase; Virtual screening.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology*
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Cytokines / antagonists & inhibitors*
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Cytokines / biosynthesis
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Dose-Response Relationship, Drug
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Drug Discovery*
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Mice
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Molecular Docking Simulation*
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Molecular Structure
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Monoacylglycerol Lipases / antagonists & inhibitors*
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Monoacylglycerol Lipases / metabolism
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RAW 264.7 Cells
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / biosynthesis
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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Cytokines
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Enzyme Inhibitors
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Lipopolysaccharides
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RNA, Messenger
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Monoacylglycerol Lipases