| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
IC50: 80 nM (MAGL)[1]
MAGL-IN-1 selectively targets monoacylglycerol lipase (MAGL), a key enzyme in the endocannabinoid system. It is a potent and selective inhibitor with an IC50 of 80 nM. MAGL is responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. By blocking this enzyme, MAGL-IN-1 elevates 2-AG levels, providing a tool to study the pharmacological effects of endocannabinoid enhancement. |
|---|---|
| ln Vitro |
In all examined cancer cell lines, MAGL-IN-1 (Compound 23) (0.02 - 200 μM; 96 hours) significantly inhibits cell viability, with an IC50 ranging from 7.9 to 57 μM [1]. Using 4-nitrobenzene acetate, MAGL-IN-1 (0.125-1 μM; 30 minutes) binds MAGL in a competitive manner with a Ki of 39 nM [1]. At 10 μM, MAGL-IN-1 (10 μM; 90 min) [1]. In U937 cells, MAGL-IN-1 (1 nM-100 μM; 15 min) inhibits [3H]2-oleoylglycerol (2-OG) hydrolysis in a concentration-dependent manner with an IC50 of 193 nM [1]. With an IC50 of 2.1 μM, MAGL-IN-1 (0.01-30 μM; 15 min) inhibits 2-OG hydrolysis in mouse meningeal preparations in a concentration-dependent manner [1].
In vitro, MAGL-IN-1 is a potent and selective monoacylglycerol lipase (MAGL) inhibitor with an IC50 of 80 nM. It effectively blocks MAGL activity in cell-based assays, which has been shown to exhibit anti-proliferative effects against human breast, colorectal, and ovarian cancer cells. This makes it a useful tool for studying the role of MAGL and the endocannabinoid 2-AG in cancer cell biology. MAGL-IN-1 also blocks MAGL in in vivo assays. |
| ln Vivo |
In mouse plasma and brain levels, MAGL (Compound 23) (50 mg/kg; single ip) raises 2-AG levels without changing levels of AEA, arachidonic acid, or prostate[1].
In vivo activity data for MAGL-IN-1 is not detailed in the provided sources. However, as a reversible, competitive inhibitor of MAGL, it is hypothesized to produce effects similar to other MAGL inhibitors, such as reducing pain, inflammation, and impacting cancer progression. Researchers would typically administer it via intraperitoneal or oral routes to animal models to measure its impact on 2-AG levels in the brain and its effects in disease models. Formal in vivo studies are needed to confirm its specific efficacy. |
| Enzyme Assay |
To determine its enzymatic activity, a cell-free MAGL activity assay is performed. Recombinant human MAGL is incubated in a reaction buffer with varying concentrations of MAGL-IN-1 (e.g., 0.1-1000 nM). The reaction is initiated by adding the substrate 2-arachidonoylglycerol (2-AG) or a fluorogenic substrate. The reaction proceeds for a set time at room temperature, and the release of arachidonic acid (or a fluorescent product) is quantified. The IC50 is calculated by fitting a dose-response curve, which has been determined to be 80 nM.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: HCT116, MDA-MB-231, CAOV3, OVCAR3, SKOV3, and MRC5 cells Tested Concentrations: 0.02-200 μM Incubation Duration: 96 hrs (hours) Experimental Results: Inhibited the growth of human breast MDA-MB-231 , colorectal HCT116, and ovarian CAOV3, OVCAR3, and SKOV3 cancer cells, with IC50s of 7.9, 21, 25, 57, and 15 μM, respectively. Was inactive against MRC5 (IC50>100 μM). Cancer cell proliferation assays are used to assess the cellular efficacy of MAGL-IN-1. Human breast (e.g., MCF-7), colorectal (e.g., HCT116), and ovarian (e.g., SKOV3) cancer cells are seeded in 96-well plates. They are treated with varying concentrations of MAGL-IN-1 (e.g., 0.01-100 uM) for 48-72 hours. Cell proliferation and viability are then measured using a standard MTT or CellTiter-Glo luminescent assay. The results can be used to correlate MAGL inhibition with reduced cancer cell growth. |
| Animal Protocol |
Animal/Disease Models: Male C57BL6 mice, 8-10 weeks old[1]
Doses: 50 mg/kg Route of Administration: intraperitoneal (ip) injection; once Experimental Results: Increased 2-AG levels in the brain and plasma. In vivo studies for MAGL-IN-1 could be performed using a xenograft mouse model of cancer. Mice are subcutaneously implanted with human cancer cells (e.g., HCT116 colorectal cancer cells). When tumors reach a certain volume, mice are randomized and treated with MAGL-IN-1 or a vehicle control. The compound would be formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline and administered via intraperitoneal injection at doses of 10-100 mg/kg once daily. Tumor volume is measured with calipers twice weekly to assess the anti-tumor efficacy. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for MAGL-IN-1 is limited. The compound has a molecular weight of 369.43 g/mol. For in vivo use, it is typically formulated in a co-solvent vehicle (e.g., DMSO, PEG300, saline). Researchers should perform pilot PK studies to determine key parameters such as half-life, Cmax, and oral bioavailability in their specific animal model before conducting efficacy studies.
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| Toxicity/Toxicokinetics |
Publicly available toxicology data for MAGL-IN-1 is limited. In cell-based cancer proliferation assays, MAGL-IN-1 exhibits anti-proliferative effects, meaning it reduces the viability of cancer cells. This effect is concentration-dependent. The selectivity of the compound suggests that its effects are primarily mediated through MAGL inhibition. Standard safety precautions for handling research chemicals should be followed.
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| References | |
| Additional Infomation |
MAGL-IN-1 is a research-grade compound and is not approved for clinical use. It is a valuable and potent tool for studying the biology of monoacylglycerol lipase (MAGL) and the endocannabinoid 2-AG. Its applications are primarily in the fields of cancer biology, neurobiology (pain, anxiety), and inflammation. 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 |
C22H24FNO3
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|---|---|
| Molecular Weight |
369.43
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| Exact Mass |
369.174
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| CAS # |
2324160-91-8
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| PubChem CID |
138319671
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
558.9±50.0 °C at 760 mmHg
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| Flash Point |
291.8±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.585
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| LogP |
3.17
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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 |
27
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| Complexity |
522
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)C1=CC=C(C=C1)C(=O)C2CCN(CC2)C(=O)C3=C(C=CC(=C3)O)F
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| InChi Key |
WUUBZNFATQKRPH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24FNO3/c1-14(2)15-3-5-16(6-4-15)21(26)17-9-11-24(12-10-17)22(27)19-13-18(25)7-8-20(19)23/h3-8,13-14,17,25H,9-12H2,1-2H3
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| Chemical Name |
[1-(2-fluoro-5-hydroxybenzoyl)piperidin-4-yl]-(4-propan-2-ylphenyl)methanone
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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: 62.5 mg/mL (169.18 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.63 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (5.63 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 20.8 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: ≥ 2.08 mg/mL (5.63 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 | 2.7069 mL | 13.5344 mL | 27.0687 mL | |
| 5 mM | 0.5414 mL | 2.7069 mL | 5.4137 mL | |
| 10 mM | 0.2707 mL | 1.3534 mL | 2.7069 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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