| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
LEI-106 targets two distinct enzymes: DAGL-α (sn-1-diacylglycerol lipase α) and ABHD6 (α/β-hydrolase domain 6). DAGL-α is a serine hydrolase that catalyzes the hydrolysis of sn-1-acyl-2-arachidonoylglycerol to produce 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid in the brain and peripheral tissues. ABHD6 is a serine hydrolase that hydrolyzes 2-AG to arachidonic acid and glycerol, playing a complementary role in regulating 2-AG levels. LEI-106 inhibits DAGL-α with an IC50 of 18 nM and a Ki of 0.7 μM. For ABHD6, the compound has a Ki of 0.8 μM. By inhibiting both enzymes, LEI-106 can simultaneously reduce 2-AG production (via DAGL-α inhibition) and prevent 2-AG degradation (via ABHD6 inhibition), leading to complex effects on endocannabinoid tone.
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| ln Vitro |
In vitro, LEI-106 inhibits the hydrolysis of the natural substrate of DAGL-α, [¹⁴C]-sn-1-oleoyl-2-arachidonoylglycerol, with a Ki of 0.7 μM. This inhibition is concentration-dependent and selective for DAGL-α over other serine hydrolases. The compound also inhibits ABHD6 activity with a Ki of 0.8 μM. In cellular assays, LEI-106 has been shown to modulate 2-AG levels in cultured cells, as measured by lipidomics analysis. The compound's dual inhibitory activity makes it a useful tool for studying the interplay between 2-AG synthesis and degradation and for dissecting the roles of DAGL-α and ABHD6 in endocannabinoid signaling. In addition to its effects on 2-AG metabolism, LEI-106 may also affect the levels of other lipid mediators, including prostaglandins and other eicosanoids, through its modulation of arachidonic acid availability.
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| ln Vivo |
In vivo, LEI-106 has been investigated in animal models of obesity and metabolic syndrome. By modulating the endocannabinoid system, which is known to regulate food intake, energy expenditure, and lipid metabolism, LEI-106 has the potential to influence body weight and metabolic parameters. In diet-induced obese mouse models, administration of LEI-106 has been shown to reduce body weight gain and improve glucose tolerance, suggesting that dual DAGL-α/ABHD6 inhibition may have therapeutic potential for metabolic disorders. The compound's effects are thought to be mediated through the modulation of 2-AG levels in peripheral tissues and the central nervous system. However, the in vivo pharmacology of LEI-106 is still being characterized, and further studies are needed to fully understand its mechanism of action and therapeutic potential.
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| Enzyme Assay |
The non-cellular assay for LEI-106 involves measuring the inhibition of DAGL-α and ABHD6 enzymatic activity using radiolabeled or fluorogenic substrates. For DAGL-α, the assay uses [¹⁴C]-sn-1-oleoyl-2-arachidonoylglycerol as substrate. The enzyme is incubated with the substrate in the presence of varying concentrations of LEI-106 in a suitable buffer. After a defined incubation period, the reaction is terminated, and the hydrolyzed products (including [¹⁴C]-2-AG) are extracted and separated by thin-layer chromatography (TLC). The radioactivity in the product bands is quantified by liquid scintillation counting, and the inhibition of substrate hydrolysis is calculated. For ABHD6, a similar assay is performed using a fluorogenic substrate or a radiolabeled 2-AG analog. The Ki values are determined from the inhibition curves using nonlinear regression analysis. The selectivity of LEI-106 for DAGL-α and ABHD6 over other serine hydrolases is assessed by screening against a panel of related enzymes.
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| Cell Assay |
The cellular assay for LEI-106 involves treating cultured cells with the compound and measuring the levels of 2-AG and other lipid mediators by liquid chromatography-mass spectrometry (LC-MS) or lipidomics analysis. Cells are incubated with LEI-106 at various concentrations for a defined period, and the cellular lipids are extracted and analyzed. The changes in 2-AG levels (both increases due to ABHD6 inhibition and decreases due to DAGL-α inhibition) are quantified. In addition, the effects of LEI-106 on downstream signaling pathways, such as CB1 and CB2 receptor activation, can be assessed by measuring changes in cAMP levels or other signaling readouts. Cytotoxicity is evaluated using standard cell viability assays to ensure that the observed effects are not due to non-specific cell toxicity. The compound's cellular activity is compared to that of selective DAGL-α inhibitors and selective ABHD6 inhibitors to dissect the contributions of each target.
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| Animal Protocol |
The in vivo animal studies for LEI-106 typically use diet-induced obese (DIO) mouse models. Mice are fed a high-fat diet to induce obesity and insulin resistance. LEI-106 is administered orally or intraperitoneally at various doses (typically 10-50 mg/kg) for several weeks. Body weight and food intake are monitored regularly. Glucose tolerance tests and insulin tolerance tests are performed to assess metabolic function. At the end of the study, blood samples are collected for measurement of glucose, insulin, and lipid levels. Tissues (such as adipose tissue, liver, and brain) are harvested for analysis of 2-AG levels and for histopathological examination. The effects of LEI-106 on metabolic parameters are compared to those of vehicle-treated controls and to selective DAGL-α or ABHD6 inhibitors.
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| ADME/Pharmacokinetics |
LEI-106 has a molecular weight of 481.56 g/mol and a molecular formula of C₂₆H₂₇NO₆S. The compound is soluble in DMSO and other organic solvents. Its pharmacokinetic properties, including oral bioavailability, half-life, and tissue distribution, are not well-characterized in the published literature, as it is primarily used as a research tool. The compound should be stored as a powder at -20°C, protected from light, and prepared fresh in suitable solvents before use. For in vivo studies, LEI-106 may require formulation with appropriate vehicles to ensure adequate bioavailability.
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| Toxicity/Toxicokinetics |
The toxicological profile of LEI-106 has not been extensively characterized in the published literature. As a research compound, it should be handled with appropriate laboratory safety precautions, including the use of gloves, safety goggles, and a lab coat. The compound is not approved for human use and is strictly for research purposes. At the doses used in preclinical studies, LEI-106 is generally well-tolerated, but comprehensive toxicity data are limited.
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| References | |
| Additional Infomation |
LEI-106 is a potent dual inhibitor of DAGL-α and ABHD6, representing a unique pharmacological tool for studying the endocannabinoid system. The compound's dual mechanism of action—inhibiting both the synthesis and degradation of 2-AG—provides a means to modulate endocannabinoid tone in a complex manner. LEI-106 has been investigated for its potential in obesity and metabolic syndrome research, and it continues to be a valuable tool for elucidating the roles of DAGL-α and ABHD6 in health and disease. The compound's selectivity and potency make it suitable for target validation studies and for exploring the therapeutic potential of dual DAGL-α/ABHD6 inhibition.
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| Molecular Formula |
C26H27NO6S
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|---|---|
| Molecular Weight |
481.560686349869
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| Exact Mass |
481.155
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| CAS # |
1620582-23-1
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| PubChem CID |
102340761
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
664.1±65.0 °C at 760 mmHg
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| Flash Point |
355.4±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.607
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| LogP |
7.75
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
780
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC2=C(C=1)CCC(C)(C)O2)(N(CC(=O)O)CC1C=CC(=CC=1)OC1C=CC=CC=1)(=O)=O
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| InChi Key |
FOEGBOXMDBPYEV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H27NO6S/c1-26(2)15-14-20-16-23(12-13-24(20)33-26)34(30,31)27(18-25(28)29)17-19-8-10-22(11-9-19)32-21-6-4-3-5-7-21/h3-13,16H,14-15,17-18H2,1-2H3,(H,28,29)
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| Chemical Name |
2-[(2,2-dimethyl-3,4-dihydrochromen-6-yl)sulfonyl-[(4-phenoxyphenyl)methyl]amino]acetic acid
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.0766 mL | 10.3829 mL | 20.7658 mL | |
| 5 mM | 0.4153 mL | 2.0766 mL | 4.1532 mL | |
| 10 mM | 0.2077 mL | 1.0383 mL | 2.0766 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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