In Vitro: O-Aryl carbamate and N-aryl urea inhibitors have been shown to irreversibly inhibit FAAH by carbamylation of the enzyme’s serine nucleophile. SA57 exhibits clear time-dependent inhibition of FAAH and MAGL, suggesting a covalent mechanism of inactivation, presumably through carbamylation of the active site serine nucleophiles of these enzymes.
In Vivo: SA57 (0.01-12.5 mg/kg; intraperitoneal injection; for 2 hours; C57Bl/6 mice) treatment shows distinct dose-responsive activity against brain serine hydrolases (FAAH, MAGL and ABHD6) in vivo.