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WWL123

Alias: WWL 123; WWL-123; WWL123
Cat No.:V28232 Purity: ≥98%
WWL123, a carbamate compound, is a potent and specific ABHD6 inhibitor.
WWL123
WWL123 Chemical Structure CAS No.: 1338574-83-6
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
WWL123, a carbamate compound, is a potent and specific ABHD6 inhibitor. WWL123 may be utilized to study inflammation, metabolic disorders (and type 2 diabetes) and epilepsy.
WWL123 is a potent, selective, and brain-penetrant inhibitor of α/β-hydrolase domain 6 (ABHD6), a serine hydrolase involved in the metabolism of endocannabinoids. It has an IC50 of 0.43 µM for ABHD6 and demonstrates >10-fold selectivity for ABHD6 compared to a panel of ~35 other serine hydrolases. WWL123 is used as a research tool to study the role of ABHD6 in various physiological and pathological processes, including inflammation, metabolic disorders, epilepsy, and Huntington's disease.
Biological Activity I Assay Protocols (From Reference)
Targets
WWL123 targets α/β-hydrolase domain 6 (ABHD6), a serine hydrolase that catalyzes the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). By inhibiting ABHD6, WWL123 increases the levels of 2-AG, which activates cannabinoid receptors CB1 and CB2. This leads to the modulation of various signaling pathways involved in inflammation, pain, and neuronal excitability. WWL123 is a brain-penetrant compound, allowing it to exert its effects in the central nervous system.
ln Vitro
WWL123 is a potent inhibitor of ABHD6 with an IC50 of 0.43 µM. It is selective for ABHD6, showing >10-fold selectivity over a panel of ~35 other serine hydrolases. The compound is brain-penetrant, making it suitable for studying the role of ABHD6 in the central nervous system.
ln Vivo
WWL123 has been shown to decrease seizure incidence in a genetic mouse model of juvenile Huntington's disease as well as in chemically-induced epilepsy models. It blocks pentylenetetrazole (PTZ)-induced seizures in healthy mice and spontaneous seizures in R6/2 mice. These findings demonstrate the in vivo efficacy of WWL123 in models of epilepsy and Huntington's disease.
Enzyme Assay
The in vitro enzyme inhibition assay for WWL123 typically involves measuring its inhibitory activity against ABHD6 using a fluorogenic substrate. The compound is incubated with the enzyme and the substrate, and the release of the fluorescent product is measured. The IC50 value is determined from the dose-response curve. Selectivity is assessed by testing the compound against a panel of other serine hydrolases.
Cell Assay
The in vitro cellular assay for WWL123 typically involves culturing cells that express ABHD6, such as neurons or microglia. Cells are treated with varying concentrations of the compound, and the levels of 2-AG are measured by LC-MS/MS. The compound's effects on downstream signaling pathways, such as the activation of cannabinoid receptors, can also be assessed.
Animal Protocol
In vivo animal studies for WWL123 typically involve the use of mouse models of epilepsy or Huntington's disease. In the PTZ-induced seizure model, mice are administered the compound via intraperitoneal injection before PTZ treatment, and the latency to seizure onset and seizure severity are assessed. In the R6/2 mouse model of Huntington's disease, the compound is administered chronically, and spontaneous seizures are monitored.
ADME/Pharmacokinetics
WWL123 has a molecular weight of 436.5 g/mol and a molecular formula of C28H24N2O3. The IUPAC name is [1,1'-biphenyl]-4-yl ([1,1'-biphenyl]-3-ylmethyl)(methyl)carbamate. The compound is a crystalline solid with a purity of ≥95%. It is soluble in DMSO (1 mg/mL) and should be stored at -20°C. Further detailed PK parameters are not available in the public domain.
Toxicity/Toxicokinetics
Specific toxicology data for WWL123 are not available in the public domain. The compound is intended for research use only and should be handled with appropriate laboratory safety precautions. Standard safety assessments would be required before any clinical application. Researchers should consult the safety data sheet for detailed handling and disposal information.
References

[1]. Revisiting 1,3,4-Oxadiazol-2-ones: Utilization in the Development of ABHD6 Inhibitors. Bioorg Med Chem. 2015 Oct 1;23(19):6335-45.

Additional Infomation
WWL123 is a potent, selective, and brain-penetrant inhibitor of α/β-hydrolase domain 6 (ABHD6). It has an IC50 of 0.43 µM for ABHD6. It is used as a research tool to study the role of ABHD6 in inflammation, metabolic disorders, epilepsy, and Huntington's disease. It has been shown to decrease seizure incidence in mouse models. It has not yet entered clinical trials and is strictly for preclinical research purposes.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C28H24N2O3
Molecular Weight
436.51
Exact Mass
436.178
CAS #
1338574-83-6
PubChem CID
90209976
Appearance
White to off-white solid powder
Density
1.2±0.1 g/cm3
Boiling Point
646.2±55.0 °C at 760 mmHg
Flash Point
344.6±31.5 °C
Vapour Pressure
0.0±1.9 mmHg at 25°C
Index of Refraction
1.631
LogP
5.2
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
7
Heavy Atom Count
33
Complexity
631
Defined Atom Stereocenter Count
0
SMILES
CN(CC1=CC(=CC=C1)C2=CC=CC=C2)C(=O)OC3=CC=C(C=C3)C4=CC=C(C=C4)C(=O)N
InChi Key
UUJGYRHAOHORFC-UHFFFAOYSA-N
InChi Code
InChI=1S/C28H24N2O3/c1-30(19-20-6-5-9-25(18-20)21-7-3-2-4-8-21)28(32)33-26-16-14-23(15-17-26)22-10-12-24(13-11-22)27(29)31/h2-18H,19H2,1H3,(H2,29,31)
Chemical Name
[4-(4-carbamoylphenyl)phenyl] N-methyl-N-[(3-phenylphenyl)methyl]carbamate
Synonyms
WWL 123; WWL-123; WWL123
HS Tariff Code
2934.99.9001
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 Data
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
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.2909 mL 11.4545 mL 22.9090 mL
5 mM 0.4582 mL 2.2909 mL 4.5818 mL
10 mM 0.2291 mL 1.1454 mL 2.2909 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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