DO34

DO34 is a highly potent, selective and centrally active diacylglycerol lipase (DAGL) inhibitor, with an IC₅₀ of 6 nM for DAGLα conversion of SAG to 2-AG, and an IC₅₀ for DAGLβ. IC50 & Target:IC50: 6 nM (DAGLα), 3-8 nM (DAGLβ)^[1]. In Vitro:DO34 is a highly potent, selective and centrally active DAGL inhibitor, with an IC₅₀ of 6 nM for DAGLα conversion of SAG to 2-AG, as determined using a real-time, fluorescence-based natural substrate assay with membrane lysates from HEK293T cells expressing recombinant human DAGLα. It is also confirmed that and DO34 is a potent inhibitor of DAGLβ with IC₅₀ of 3-8 nM^[1]. In Vivo:DO34 (compound 39) prevents fasting-induced refeeding of mice, which is typical cannabinoid CB₁-receptor mediated behavior. DO34 (comound 39) reduces brain 2-AG levels in dose- and time dependent manner^[2]. DO34 could block the tonic CB₁ activation. AM251 significantly increases basal PF-EPSCs in MAGL-TKO mice, and the effect of AM251 is blocked by the DAGL inhibitor DO34^[3].