SA57

SA57 is a potent, selective FAAH inhibitor with IC₅₀s of 3.2 nM and 1.9 nM for mouse and human FAAH. SA57 also inhibits the 2-arachidonoylglycerol hydrolases MAGL (IC₅₀s of 410 nM and 1.4 μM for mouse and human MAGL) and mouse α/β-hydrolase domain-containing protein 6 (mABHD6; IC₅₀ of 850 nM), but not other brain serine hydrolases^[1][2]. IC50 & Target: IC50: 3.2 nM (Mouse FAAH) and 1.9 nM (Human FAAH); 410 nM (Mouse MAGL) and 1.4 μM (Human MAGL); 850 nM (Mouse ABHD6)^[1] 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^[1]. 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^[1].