| Identification | Back Directory | [Name]
DO-34
(DO34) | [CAS]
1848233-58-8 | [Synonyms]
DO-34
(DO34)
1-Piperazinecarboxylic acid, 3-(phenylmethyl)-4-[[4-[4-(trifluoromethoxy)phenyl]-1H-1,2,3-triazol-1-yl]carbonyl]-, 1,1-dimethylethyl ester
DO34 3-(Phenylmethyl)-4-[[4-[4-(trifluoromethoxy)phenyl]-1H-
1,2,3-triazol-1-yl]carbonyl]-1-piperazinecarboxylic acid
1,1-dimethylethyl ester | [Molecular Formula]
C26H28F3N5O4 | [MDL Number]
MFCD31807614 | [MOL File]
1848233-58-8.mol | [Molecular Weight]
531.53 |
| Chemical Properties | Back Directory | [Boiling point ]
611.4±65.0 °C(Predicted) | [density ]
1.32±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : ≥ 100 mg/mL (188.14 mM) | [form ]
Solid | [pka]
-0.68±0.70(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
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. | [Biological Activity]
DO34 is a brain-penetrantselective and highly potent diacylglycerol lipase inhibitor (recom human DAGLα/β pIC50 = 8.2/8.1 by SAG hydrolysis; mouse brain DAGLα/β pIC50 = 9.1-9.3/8.6 by ABPP ReDiMe) with detectable off-target activity toward only ABHD6 & PLA2G7 among all mouse brain serine hydrolases and little affinity toward cannabinoid receptors CB1/2. DO34 blocks depolarization-induced suppression of excitation (DSE IC50 = 0.18 μM) and inhibition (100% DSI blockage at 1 μM) in mouse cerebellar and hippocampal slices ex vivoand attenuate LPS-induced neuroinflammatory responses by lowering brain 2-AG & PGE2 level in mice in vivo (50 mg/kgi.p). | [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]. | [References]
[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. DOI:10.1073/pnas.1522364112
[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. DOI:10.1021/acs.jmedchem.6b01482
[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. DOI:10.1038/srep35829 |
|
| Company Name: |
Merck KGaA
|
| Tel: |
(+86) 21 2033 8288 |
| Website: |
http://www.sigmaaldrich.cn |
|