AM9053

AM9053 is a small molecule inhibitor of **N-acylethanolamine acid amidase (NAAA)**, a lysosomal enzyme responsible for the degradation of bioactive N-acylethanolamines (NAEs) such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). These endogenous lipids possess significant anti-inflammatory and analgesic properties. By inhibiting NAAA, AM9053 prevents the hydrolysis of these substrates, thereby increasing their local concentrations and enhancing their protective signaling. Preclinical research, particularly from the University of Naples Federico II, has demonstrated that AM9053 can modulate macrophage activity and normalize IL-23 signaling in the gut. This mechanism has shown promise in reducing intestinal fibrosis and stricture formation in models of Crohn's disease, identifying NAAA as a potential therapeutic target for managing complications of inflammatory bowel disease.