ARN726 is an inhibitor of N-acylethanolamine acid amidase (NAAA; IC50s = 27 and 63 nM for the human and rat enzyme, respectively).1 It is selective for NAAA over fatty acid amide hydrolase (FAAH) and acid ceramidase (IC50s = >100 and 12.5 μM, respectively), as well as a panel of 28 lipid metabolism- and inflammation-related enzymes at 10 μM. ARN726 (1-30 mg/kg) decreases lung myeloperoxidase activity and pleural exudate TNF-α levels in a mouse model of carrageenan-induced lung inflammation. It inhibits NAAA and reverses complete Freund's adjuvant-induced decreases in palmitoyl ethanolamide and oleoyl ethanolamide levels in inflamed paw tissue in a rat model of arthritis.2
References
1. Ribeiro, A., Pontis, S., Mengatto, L., et al. . Chem. Biol. 10, 1838-1846 (2015).
2. Bonezzi, F.T., Sasso, O., Pontis, S., et al. An important role for N-acylethanolamine acid amidase in the complete Freund's adjuvant rat model of arthritis. J. Pharmacol. Exp. Ther. 356(3), 656-663 (2016).