| Bioactivity | 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. | ||||||||||||
| Target | IC50: 6 nM (DAGLα), 3-8 nM (DAGLβ). | ||||||||||||
| Invitro | 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]. | ||||||||||||
| Name | DO34 | ||||||||||||
| CAS | 1848233-58-8 | ||||||||||||
| Formula | C26H28F3N5O4 | ||||||||||||
| Molar Mass | 531.53 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Ogasawara D, et al. Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition. Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):26-33. [2]. Deng H, et al. Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding. J Med Chem. 2017 Jan 12;60(1):428-440. [3]. Liu X, et al. Coordinated regulation of endocannabinoid-mediated retrograde synaptic suppression in the cerebellum by neuronal and astrocytic monoacylglycerol lipase. Sci Rep. 2016 Oct 24;6:35829. |