| Size | Price | Stock | Qty |
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| 1mg |
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| 10mg |
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| Targets |
MAGL-IN-4 targets monoacylglycerol lipase (MAGL) with high potency, exhibiting an IC50 of 6.2 nM. It is a selective and reversible inhibitor. MAGL is the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain. By inhibiting MAGL, MAGL-IN-4 enhances endogenous cannabinoid signaling through increased 2-AG levels, making it a powerful tool for studying the CNS effects of the endocannabinoid system.
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| ln Vitro |
Compound 4f, MAGL-IN-4, exhibits a high LLE of 5.9 and a logD of 2.3 for MAGL[1]. Regarding the similarly related serine hydrolases (FAAH and ABHD6; all IC50>10000 nM), MAGL-IN-4 shows no inhibition. Regarding cannabinoid receptors, MAGL-IN-4 exhibits negligible binding potentials (19% for CB1 and 5% for CB2 at 10 μM) and a low hERG liability (14.4 percent inh. at 10 μM, manual patch clamp, without BSA)[1].
In vitro, MAGL-IN-4 is a potent and selective inhibitor of monoacylglycerol lipase (MAGL), with an IC50 of 6.2 nM. This high level of potency, coupled with its reversibility and selectivity, makes it one of the most effective tool compounds for probing the function of the MAGL enzyme in biochemical and cellular assays. It is confirmed to block MAGL in cell-based assays. |
| ln Vivo |
In C57BL/6J mice, MAGL-IN-4 (compound 4f; 0.1-10 mg/kg; oral; single dose) causes a considerable decrease in arachidonic acid (AA) from 0.3 mg/kg and a large increase in 2-AG[1].
In vivo, MAGL-IN-4 is orally active and can penetrate the blood-brain barrier (BBB), a critical property for studying central nervous system (CNS) targets. Its primary mechanism is to enhance endogenous cannabinoid signaling by selectively inhibiting MAGL, which leads to increased levels of 2-arachidonoylglycerol (2-AG) in the brain. This profile makes it suitable for evaluating the therapeutic potential of MAGL inhibition in animal models of pain, anxiety, and neurodegenerative diseases. |
| Enzyme Assay |
For in vitro enzyme activity assays, recombinant human MAGL is incubated in an assay buffer with varying concentrations of MAGL-IN-4 (e.g., 0.01-1000 nM). The reaction is initiated by the addition of a fluorogenic substrate (e.g., arachidonoyl-7-hydroxy-6-methoxy-4-methylcoumarin ester). The increase in fluorescence, proportional to MAGL activity, is measured continuously in a plate reader. The IC50 is calculated by plotting the initial reaction velocity against the inhibitor concentration. Published data confirm an IC50 of 6.2 nM.
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| Cell Assay |
For cell-based target engagement assays, MAGL-IN-4 can be tested in neuroblastoma cell lines (e.g., Neuro-2a) or primary cortical neurons. Cells are treated with increasing concentrations of MAGL-IN-4 (e.g., 0.1-100 nM) for 1-4 hours. Cell lysates are then prepared, and the residual MAGL activity is measured using a fluorogenic substrate as described in the cell-free protocol. This demonstrates the compound's ability to engage and inhibit its target in an intact cellular environment. The concentration required for cellular inhibition is often higher than the biochemical IC50.
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| Animal Protocol |
For in vivo efficacy studies, MAGL-IN-4 is formulated in a suitable oral vehicle (e.g., 0.5% methylcellulose or 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered orally by gavage to rodents. To demonstrate BBB penetration and target engagement, animals are dosed with MAGL-IN-4 (e.g., 0.1-10 mg/kg). After 1-4 hours, animals are euthanized, and brains are collected. Brain tissue is homogenized, and the levels of 2-arachidonoylglycerol (2-AG) are measured by LC-MS/MS. A significant increase in 2-AG levels compared to a vehicle-treated control confirms BBB penetration and on-target activity.
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| ADME/Pharmacokinetics |
MAGL-IN-4 has excellent properties for an orally available CNS tool compound. It demonstrates good oral absorption and blood-brain barrier penetration, as evidenced by its ability to elevate brain 2-AG levels. While detailed PK parameters (Cmax, T1/2, AUC) are not provided in the search results, its oral activity and BBB penetration suggest a favorable pharmacokinetic profile. Researchers should consult the primary literature for specific PK data in their model species.
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| Toxicity/Toxicokinetics |
Published toxicology data for MAGL-IN-4 is limited. In cell-based assays at concentrations used for target inhibition (up to ~100 nM), no overt cytotoxicity is reported. The selectivity of the compound suggests a low risk of off-target effects. In animal studies at effective oral doses (typically in the low mg/kg range), no acute toxicity has been reported. For research use only.
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| References | |
| Additional Infomation |
MAGL-IN-4 is a research-grade compound and is not approved for clinical use. It is one of the most potent and advanced tool compounds available for studying the role of MAGL in the brain. Its excellent properties (high potency, oral activity, BBB penetration) make it a valuable tool for validating MAGL as a therapeutic target for CNS disorders. The compound should be stored as a powder at -20degC, protected from light and moisture. For research use only.
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| Molecular Formula |
C18H21CLN2O4
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| Molecular Weight |
364.82
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| Exact Mass |
364.118
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| CAS # |
2135785-20-3
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| PubChem CID |
130475870
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| Appearance |
White to off-white solid powder
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| LogP |
1.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
545
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1[C@]2(COC(=O)N2)C[C@H]1C(N1CC(OCC2=CC=C(C)C(Cl)=C2)C1)=O
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| InChi Key |
AKBHYCHPWZPGAH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21ClN2O4/c1-11-2-3-12(4-15(11)19)9-24-14-7-21(8-14)16(22)13-5-18(6-13)10-25-17(23)20-18/h2-4,13-14H,5-10H2,1H3,(H,20,23)
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| Chemical Name |
2-[3-[(3-chloro-4-methylphenyl)methoxy]azetidine-1-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one
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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: 100 mg/mL (274.11 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.85 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 (6.85 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 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 (6.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7411 mL | 13.7054 mL | 27.4108 mL | |
| 5 mM | 0.5482 mL | 2.7411 mL | 5.4822 mL | |
| 10 mM | 0.2741 mL | 1.3705 mL | 2.7411 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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