| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
The primary target of JZP-361 is monoacylglycerol lipase (MAGL), the principal enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL is a serine hydrolase that terminates 2-AG signaling by converting it to arachidonic acid and glycerol. JZP-361 is a potent, reversible, and selective MAGL inhibitor with an IC₅₀ of 46 nM. It shows 35-fold and 150-fold selectivity over FAAH and ABHD6, respectively. The compound also retains H1 antagonistic affinity (pA2 = 6.81) but does not show cannabinoid receptor activity.
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| ln Vitro |
Compared to human recombinant fatty acid amide hydrolase (hFAAH, IC50 = 7.24 μM) and human α/β-hydrolase-6 (hABHD6, IC50 = 1.79 μM), JZP-361 exhibits selectivity that is over 150 times higher [1]. While JZP-361 shows minimal cannabinoid receptor activity, it maintains its H1 antagonistic affinity (pA2 = 6.81) at doses ≤10 μM [1]. Excellent interactions are seen at the hMAGL active site of JZP-361, including a significant hydrogen bonding between the carbonyl oxygen and the oxygen anion hole [1].
In vitro, JZP-361 inhibits human recombinant MAGL with an IC₅₀ of 46 nM. It exhibits 35-fold and 150-fold higher selectivity over human FAAH (IC₅₀ = 7.24 μM) and ABHD6 (IC₅₀ = 1.79 μM), respectively. The compound retains H1 antagonistic affinity (pA2 = 6.81) but does not show cannabinoid receptor activity. This dual MAGL inhibitory and antihistaminergic activity makes JZP-361 a unique tool for studying the interplay between endocannabinoid and histamine signaling. |
| ln Vivo |
In vivo, JZP-361 has antihistaminergic activity and can be used for asthma research. By inhibiting MAGL, the compound would be expected to increase 2-AG levels and modulate endocannabinoid signaling in vivo. Its H1 antagonistic activity suggests potential applications in allergy and inflammation. However, specific in vivo efficacy data from animal models is not detailed in the available sources. The compound does not show cannabinoid receptor activity.
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| Enzyme Assay |
For MAGL inhibitors, standard cell-free assays involve measuring the hydrolytic activity of MAGL using a fluorogenic substrate or radiolabeled 2-oleoylglycerol. The compound is incubated with the enzyme and substrate, and the release of fluorescent or radiolabeled product is measured to determine IC₅₀ values. Selectivity for MAGL over FAAH and ABHD6 is assessed using enzyme assays for these targets.
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| Cell Assay |
For MAGL inhibitors, standard cellular assays involve treatment of cells (e.g., neuroblastoma cells or primary neurons) with the test compound for 1-4 hours. 2-AG levels in cell lysates are measured by LC-MS. MAGL activity is assessed by measuring the hydrolysis of a fluorogenic substrate in cell lysates. Effects on downstream signaling (e.g., cannabinoid receptor activation, ERK phosphorylation) are also measured. H1 antagonism is assessed using histamine receptor binding or functional assays.
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| Animal Protocol |
For in vivo evaluation of MAGL inhibitors, standard animal models include pain models, anxiety models, and models of inflammation. For asthma research, models of allergic airway inflammation are used. The compound is typically administered orally or intraperitoneally, and behavioral, biochemical, and pharmacological endpoints are assessed.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for JZP-361 is not extensively provided in the available sources. The compound has a molecular weight of 462.39 and formula C₂₅H₂₂N₆O. It has a purity of ≥98%. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability and oral bioavailability. Comprehensive PK studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
Detailed toxicology data for JZP-361 is not provided in the available sources. As a research compound targeting MAGL with additional H1 antagonistic activity, standard preclinical toxicology would be required for therapeutic development. The compound's dual activities may have both therapeutic and off-target effects that would need to be evaluated. The compound is for research use only and not for therapeutic applications.
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| References | |
| Additional Infomation |
JZP-361 is a potent, reversible, and selective inhibitor of human recombinant MAGL with an IC₅₀ of 46 nM. It exhibits 35-fold and 150-fold selectivity over FAAH (IC₅₀ = 7.24 μM) and ABHD6 (IC₅₀ = 1.79 μM), respectively. The compound retains H1 antagonistic affinity (pA2 = 6.81) but does not show cannabinoid receptor activity. No regulatory approval has been identified.
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| Molecular Formula |
C22H20CLN5O
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|---|---|
| Molecular Weight |
405.87
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| Exact Mass |
405.135
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| CAS # |
1680193-80-9
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| PubChem CID |
102596130
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
611.7±65.0 °C at 760 mmHg
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| Flash Point |
323.8±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.725
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| LogP |
3.88
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
29
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| Complexity |
645
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
GAVZCGTYRWKKDV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H20ClN5O/c23-18-5-6-19-17(12-18)4-3-16-2-1-9-25-21(16)20(19)15-7-10-27(11-8-15)22(29)28-14-24-13-26-28/h1-2,5-6,9,12-14H,3-4,7-8,10-11H2
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| Chemical Name |
[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]-(1,2,4-triazol-1-yl)methanone
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| Synonyms |
JZP361; JZP 361; JZP-361
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~307.97 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4638 mL | 12.3192 mL | 24.6384 mL | |
| 5 mM | 0.4928 mL | 2.4638 mL | 4.9277 mL | |
| 10 mM | 0.2464 mL | 1.2319 mL | 2.4638 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.
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