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Arachidonoyl glycine (NAGly) is an endogenous lipid and a structural derivative of the endocannabinoid anandamide (AEA). It is characterized by the substitution of the ethanolamine group in AEA with a glycine residue, which increases its polarity and alters its metabolic profile. NAGly is notably resistant to degradation by fatty acid amide hydrolase (FAAH) and serves as a substrate for cyclooxygenase-2 (COX-2), which metabolizes it into oxygenated products that may contribute to its biological effects. Research, including studies presented at AACR, has highlighted its potential as an anti-cancer agent due to its ability to reduce cell viability in various epithelial cancers such as melanoma, colon cancer, and tumorigenic keratinocytes. Beyond its antineoplastic properties, NAGly is a potent agonist of the G protein-coupled receptor GPR18 and has been implicated in pain modulation and inflammatory signaling.
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