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WWL-123

Cat No.:V45847 Purity: ≥98%
WWL-123 is a novel, potent andselective ABHD6 inhibitor with antiepileptic effects.
WWL-123
WWL-123 Chemical Structure CAS No.: 1338575-41-9
Product category: MAGL
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
WWL-123 is a novel, potent and selective ABHD6 inhibitor with antiepileptic effects. It inhibits ABHD6 with an IC50 of 430 nM.
WWL-123 is a novel, potent, and selective inhibitor of α/β-hydrolase domain-containing protein 6 (ABHD6) with an IC₅₀ of 430 nM. It crosses the blood-brain barrier and inhibits ABHD6 in brain parenchyma. WWL-123 exerts antiepileptic effects in pentylenetetrazole (PTZ)-induced epileptiform seizures and spontaneous seizures in R6/2 mice. It has the molecular formula C₂₈H₂₄N₂O₃ and molecular weight 436.50. WWL-123 is used in research on endocannabinoid signaling and neurological disorders.
Biological Activity I Assay Protocols (From Reference)
Targets
WWL-123 targets α/β-hydrolase domain-containing protein 6 (ABHD6), a serine hydrolase that hydrolyzes the endocannabinoid 2-arachidonoylglycerol (2-AG). ABHD6 is one of the principal enzymes responsible for regulating 2-AG levels in the brain. By inhibiting ABHD6, WWL-123 increases 2-AG levels, modulating endocannabinoid signaling. ABHD6 has also been implicated in neurological disorders, inflammation, and metabolic diseases. WWL-123 is a selective inhibitor with an IC₅₀ of 430 nM.
ln Vitro
WWL-123 inhibits ABHD6 with an IC₅₀ of 430 nM. It shows selectivity for ABHD6 over other serine hydrolases. The compound crosses the blood-brain barrier and inhibits ABHD6 in brain parenchyma. WWL-123 exerts antiepileptic effects in PTZ-induced epileptiform seizures and spontaneous seizures in R6/2 mice. These activities make it a valuable tool for studying ABHD6 biology and endocannabinoid signaling.
ln Vivo
WWL-123 exerts antiepileptic effects in vivo, suppressing seizures in both PTZ-induced and R6/2 mouse models. It crosses the blood-brain barrier and inhibits ABHD6 in brain parenchyma. The compound's in vivo efficacy in seizure models demonstrates its potential for studying neurological disorders and endocannabinoid signaling. Specific dosing and efficacy details are documented in the literature.
Enzyme Assay
The non-cellular enzyme/receptor binding assay for WWL-123 typically involves measuring ABHD6 enzymatic activity using a fluorogenic substrate. Recombinant ABHD6 enzyme is incubated with a suitable substrate (e.g., a fluorogenic ester) and varying concentrations of WWL-123. The release of fluorescent product is measured over time. IC₅₀ values are calculated from dose-response curves. Selectivity over other serine hydrolases is assessed using similar assays with panels of related enzymes.
Cell Assay
In vitro cellular assays for WWL-123 typically use neuronal cell lines or primary neurons to evaluate ABHD6 inhibition. Cells are treated with various concentrations of WWL-123, and ABHD6 activity is assessed by measuring the hydrolysis of a fluorogenic substrate or by quantifying 2-AG levels using LC-MS/MS. Cell viability is assessed using MTT or LDH assays. The compound's effects on endocannabinoid signaling can be evaluated by measuring downstream signaling markers.
Animal Protocol
In vivo animal studies for WWL-123 have demonstrated antiepileptic efficacy in PTZ-induced seizure models and in R6/2 mice (a model of Huntington's disease). WWL-123 is administered intraperitoneally or orally. Seizure incidence, latency, and severity are monitored. Brain tissue is collected to measure ABHD6 inhibition and 2-AG levels. Behavioral assessments are performed to evaluate neurological function. Detailed protocols are available in the literature.
ADME/Pharmacokinetics
Pharmacokinetic properties of WWL-123 are characterized by its ability to cross the blood-brain barrier. As a small molecule with molecular weight 436.50, it is expected to have reasonable oral bioavailability. The compound is brain-penetrant, making it suitable for studying neurological disorders. Specific PK parameters such as half-life, Cmax, and protein binding are not extensively documented.
Toxicity/Toxicokinetics
Toxicological data for WWL-123 are limited. As a research-grade compound, comprehensive toxicology studies are not available. The compound has been used in animal models at doses that exert antiepileptic effects without apparent acute toxicity. However, detailed toxicity profiles are not documented. Standard laboratory safety precautions should be observed when handling this compound.
References

[1].Daniel A Bachovchin, et al. Superfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening. Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):20941-6.

[2].Peng Zhong, et al. Genetic deletion of monoacylglycerol lipase alters endocannabinoid-mediated retrograde synaptic depression in the cerebellum. J Physiol. 2011 Oct 15;589(Pt 20):4847-55.

[3].Alipi V Naydenov, et al. ABHD6 blockade exerts antiepileptic activity in PTZ-induced seizures and in spontaneous seizures in R6/2 mice. Neuron. 2014 Jul 16;83(2):361-371

Additional Infomation
WWL-123 is a research-grade compound intended for laboratory use only. It is not approved for clinical use as a therapeutic agent. Its primary applications include studying ABHD6 biology and endocannabinoid signaling, investigating the role of ABHD6 in neurological disorders including epilepsy and Huntington's disease, and exploring the therapeutic potential of ABHD6 inhibitors. WWL-123 is a valuable tool for neuroscience and drug discovery research.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C28H24N2O3
Molecular Weight
436.501767158508
Exact Mass
436.178
CAS #
1338575-41-9
PubChem CID
53364549
Appearance
White to off-white solid powder
Density
1.2±0.1 g/cm3
Boiling Point
655.2±55.0 °C at 760 mmHg
Flash Point
350.1±31.5 °C
Vapour Pressure
0.0±2.0 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
639
Defined Atom Stereocenter Count
0
SMILES
CN(CC1=CC(=CC=C1)C2=CC=CC=C2)C(=O)OC3=CC=CC(=C3)C4=CC=C(C=C4)C(=O)N
InChi Key
QKMMESWNJMOPIF-UHFFFAOYSA-N
InChi Code
InChI=1S/C28H24N2O3/c1-30(19-20-7-5-10-24(17-20)21-8-3-2-4-9-21)28(32)33-26-12-6-11-25(18-26)22-13-15-23(16-14-22)27(29)31/h2-18H,19H2,1H3,(H2,29,31)
Chemical Name
[3-(4-carbamoylphenyl)phenyl] N-methyl-N-[(3-phenylphenyl)methyl]carbamate
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)
DMSO : ~50 mg/mL (~114.55 mM)
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 2.2910 mL 11.4548 mL 22.9095 mL
5 mM 0.4582 mL 2.2910 mL 4.5819 mL
10 mM 0.2291 mL 1.1455 mL 2.2910 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

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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)
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  • 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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