DO34 is a potent, selective, centrally active diacylglycerol lipase (DAGL) inhibitor (antagonist) with IC50 of 6 nM for DAGLα conversion and IC50 of 3-8 nM for DAGLβ.

Physicochemical Properties

Molecular Formula	C26H28F3N5O4
Molecular Weight	531.526836395264
Exact Mass	531.209
CAS #	1848233-58-8
Related CAS #	DO34 analog;2098969-71-0
PubChem CID	129188708
Appearance	Off-white to light yellow solid powder
LogP	5.1
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	6
Heavy Atom Count	38
Complexity	810
Defined Atom Stereocenter Count	0
SMILES	FC(OC1C=CC(=CC=1)C1=CN(C(N2CCN(C(=O)OC(C)(C)C)C[C@H]2CC2C=CC=CC=2)=O)N=N1)(F)F
InChi Key	CQGMWUWJVBKTRM-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H28F3N5O4/c1-25(2,3)38-24(36)32-13-14-33(20(16-32)15-18-7-5-4-6-8-18)23(35)34-17-22(30-31-34)19-9-11-21(12-10-19)37-26(27,28)29/h4-12,17,20H,13-16H2,1-3H3
Chemical Name	tert-butyl 3-benzyl-4-[4-[4-(trifluoromethoxy)phenyl]triazole-1-carbonyl]piperazine-1-carboxylate
Synonyms	DO 34; DO-34; DO34
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Using a real-time, fluorescence-based assay with a natural substrate, DO34 is a highly potent, selective, and centrally active inhibitor of DAGL expressed by recombinant human DAGLα. It has also been established that DO34, with an IC50 of 3–8 nM, is a strong inhibitor of DAGLβ[1].
ln Vivo	Compound 39, DO34, inhibits the common cannabinoid CB1 receptor-mediated behavior of mice's fasting-induced refeeding. Compound 39, DO34, lowers 2-AG levels in the brain in a time- and dose-dependent manner [2]. The activation of complement CB1 is blocked by DO34. In MAGL-TKO mice, AM251 markedly raises basal PF-EPSCs; the DAGL inhibitor DO34 reverses AM251's impact [3].
References	[1]. 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]. Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding. J Med Chem. 2017 Jan 12;60(1):428-440. [3]. Coordinated regulation of endocannabinoid-mediated retrograde synaptic suppression in the cerebellum by neuronal and astrocytic monoacylglycerol lipase. Sci Rep. 2016 Oct 24;6:35829.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~188.14 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 10 mg/mL (18.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 10 mg/mL (18.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 10 mg/mL (18.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8814 mL	9.4068 mL	18.8136 mL
	5 mM	0.3763 mL	1.8814 mL	3.7627 mL
	10 mM	0.1881 mL	0.9407 mL	1.8814 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.