| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
JZL 184 is the first potent, irreversible and selective inhibitor of monoacylglycerol lipase (MAGL) with IC50 of 8 NM. JZL184 is a useful tool for studying the effects of endogenous 2-AG signaling. JZL184 displays time-dependent inhibition of MAGL and exhibits >300-fold selectivity for MAGL over FAAH in vitro. JZL184 does not interact with CB1 or CB2 receptors and does not inhibit the 2-AG biosynthetic enzymes diacylglycerol lipase-αand diacylglycerol lipase-β, or the arachidonic acid–mobilizing enzyme cytosolic phospholipase A2 group IVA.
| ln Vitro |
JZL 184 inhibits the hydrolysis of oleamide (FAAH substrate) and 2-AG in brain membranes, with IC50 values of 8 nM and 4 μM, respectively. When produced in COS7 cells, recombinant MAGL and FAAH have comparable inhibitory effects[1].
|
|---|---|
| ln Vivo |
When mice treated with JZL 184 (4–40 mg/kg; intraperitoneal injection; once; C57Bl/6 mice), brain 2-AG hydrolase activity is rapidly and persistently blocked, leading to 8-fold rises in endogenous 2-AG levels, which are sustained for at least 8 hours. Mice treated with JZL 184 exhibit a striking variety of CB1-dependent behavioral responses, such as hypomotility, analgesia, and hypothermia[1]. ?JZL 184 prolongs DSE inhibition (DSI) in CA1 pyramidal neurons in hippocampus slices and Dpolarization-induced suppression of excitation (DSE) in Purkinje neurons in cerebellar slices. In comparison to rat neurons, mouse neurons exhibit a higher DSE/DSI increase when exposed to JZL 184[2].
|
| Animal Protocol |
Animal/Disease Models: Male C57Bl/6 mice (6- 8 weeks old, 20-26 g)[1]
Doses: 4 mg/kg, 8 mg/kg, 16 mg/kg, 40 mg/kg Route of Administration: intraperitoneal (ip)injection; once Experimental Results: Produced a rapid and sustained blockade of brain 2 -AG hydrolase activity in mice, resulting in 8-fold elevations in endogenous 2-AG levels that were maintained for at least 8 h. |
| References |
[1]. Long JZ, et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol. 2009 Jan;5(1):37-44.
[2]. Pan B, et al. Blockade of 2-arachidonoylglycerol hydrolysis by selective monoacylglycerol lipase inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) Enhances retrograde endocannabinoid signaling. J Pharmacol Exp Ther. 2009 Nov;331(2):591-7. |
| Molecular Formula |
C27H24N2O9
|
|
|---|---|---|
| Molecular Weight |
520.49
|
|
| CAS # |
1101854-58-3
|
|
| Related CAS # |
|
|
| SMILES |
O([H])C(C1C([H])=C([H])C2=C(C=1[H])OC([H])([H])O2)(C1C([H])=C([H])C2=C(C=1[H])OC([H])([H])O2)C1([H])C([H])([H])C([H])([H])N(C(=O)OC2C([H])=C([H])C(=C([H])C=2[H])[N+](=O)[O-])C([H])([H])C1([H])[H]
|
|
| Synonyms |
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.80 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 25.0 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: 2.5 mg/mL (4.80 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% Propylene glycol : 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9213 mL | 9.6063 mL | 19.2127 mL | |
| 5 mM | 0.3843 mL | 1.9213 mL | 3.8425 mL | |
| 10 mM | 0.1921 mL | 0.9606 mL | 1.9213 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
|---|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
