ARN-077

**ARN-077** (also known as URB913) is a potent and selective small molecule inhibitor of N-acylethanolamine acid amidase (NAAA), an enzyme responsible for the hydrolysis of N-acylethanolamines such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). With an IC50 of 7 nM against human NAAA and 11 nM against recombinant rat NAAA, it acts through a rapid, non-competitive, and reversible mechanism, preventing the degradation of these anti-inflammatory and antinociceptive lipid mediators. Topical administration has demonstrated efficacy in preclinical rodent models of inflammatory pain (carrageenan-induced hyperalgesia), neuropathic pain (chronic constriction injury), and allergic dermatitis, reducing edema, hyperalgesia, allodynia, and pruritus while normalizing tissue PEA and OEA levels. Its effects are PPAR-α dependent, as shown in knockout studies.[1][2][3][5][7]