1. Metabolic Enzyme/Protease Vitamin D Related/Nuclear Receptor Cell Cycle/DNA Damage Immunology/Inflammation
  2. Carboxylesterase (CES) PPAR Interleukin Related Mitochondrial Metabolism
  3. WWL229

WWL229 is a selective inhibitor of carboxylesterase 3 (CES3) with an IC50 1.94 μM. WWL229 attenuates LPS (HY-D1056)-induced pro-inflammatory cytokine mRNA levels, inhibits lipolysis and adipose thermogenesis, impairs mitochondrial function, and promotes lipid storage. WWL229 can be used for the research of obesity, insulin resistance, type 2 diabetes, and lung inflammation.

For research use only. We do not sell to patients.

WWL229

WWL229 Chemical Structure

CAS No. : 1338575-28-2

Size Price Stock Quantity
Liquid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
In-stock
Solution
10 mM * 1 mL in DMSO In-stock
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Based on 1 publication(s) in Google Scholar

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Description

WWL229 is a selective inhibitor of carboxylesterase 3 (CES3) with an IC50 1.94 μM. WWL229 attenuates LPS (HY-D1056)-induced pro-inflammatory cytokine mRNA levels, inhibits lipolysis and adipose thermogenesis, impairs mitochondrial function, and promotes lipid storage. WWL229 can be used for the research of obesity, insulin resistance, type 2 diabetes, and lung inflammation[1][2][3][4][5][6].

IC50 & Target[2][1]

CES3

1.94 μM (IC50)

IL-6

 

In Vitro

WWL229 (1 μM; 15 min) inhibits ~70% of CES1 activity in intact THP-1 monocytes[1].
WWL229 attenuates LPS-induced IL-6 and TNFα mRNA levels in THP-1 macrophages, both with and without exogenous 2-AG[1].
WWL229 (10-100 μM; 1 h) dose-dependently attenuates Isoproterenol (ISO) (HY-B0468)-induced lipolysis in differentiated 3T3-L1 and BAC adipocytes[2].
WWL229 (10 μM; 1 h) attenuates ISO-induced upregulation of β-oxidation genes in BAC cells, and reduces basal, proton leak, and maximal mitochondrial respiration in both 3T3-L1 and BAC adipocytes[2].
WWL229 (10 μM) downregulates thermogenic gene and protein expression in ISO-treated BAC cells, and inhibits PPAR transcriptional activity in both basal and ISO-stimulated conditions[2].
WWL229 (0.1-100 μM; 30 min) potently and selectively inhibits Ces1d activity in WT C57BL/6 wild-type mouse lung membranes[3].
WWL229 (30 μM; 1 h) has no effect on TxB2 or PGE2 levels or related gene expression in PMA-differentiated human THP-1 macrophages treated with LPS[4].
WWL229 (10 μM; 45 min) selectively inhibits Ces3 activity in adipocyte proteomes, with no inhibitory effect on Ces1f, ABHD6, or other serine hydrolases detected by ABPP-MudPIT[5].
WWL229 (5 mM; 30 min) significantly reduces ER-EM activity in Wistar rat liver ER fraction, demonstrating that the Ces1d lipolysis site is crucial for ER-EM recognition of hydrophobic aglycone substrates[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Immunofluorescence[2]

Cell Line: Differentiated 3T3-L1 and BAC adipocytes
Concentration: 10; 100 μM
Incubation Time: 1 h
Result: Had the blocking effect at all dosages, whereas a higher dose (100 μM) showed a more significant effect.
Showed a dose-dependent manner in response to ISO treatment.

Western Blot Analysis[3]

Cell Line: WT C57BL/6 wild-type mouse lung membranes
Concentration: 0.1; 0.3; 1; 3; 10; 30; 100 μM
Incubation Time: 30 min
Result: Inhibited Ces1d activity in a does-dependent manner.
Exhibited an IC50 of 2.35 μM.
In Vivo

WWL229 (30 mg/kg; i.p.; single dose) augments LPS-induced acute lung inflammation in a female-specific manner, including enhanced neutrophil infiltration and IL1b mRNA expression in female lungs[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 wild-type mice (adult female and male) with acute lung inflammation model via intraperitoneal LPS challenge[3]
Dosage: 30 mg/kg
Administration: i.p.; single dose
Result: Augmented LPS-induced serum monocyte chemoattractant protein-1 (MCP-1) levels in female mice but not male mice at 6 hours post-LPS challenge.
Enhanced LPS-induced myeloperoxidase (MPO) activity and increased Il1b mRNA levels in female mouse lungs; these effects were not observed in male mouse lungs at 6 hours post-LPS challenge.
Did not alter LPS-induced Il6 or Tnfa mRNA levels in either female or male mouse lungs, nor significantly change other serum cytokine/chemokine levels induced by LPS.
Inhibited lung carboxylesterase (Ces) activity in female mice (but not male mice) at 4 hours post-dosing; inhibited lung Ces activity in both female and male mice to a similar degree by 6 hours post-dosing.
Selectively inhibited lung Ces1d activity in vivo by ~75% at 4 hours, with no inhibition of Ces1c or monoacylglycerol lipase (Magl).
Molecular Weight

322.36

Formula

C16H22N2O5

CAS No.
Appearance

Liquid (Density: 1.196±0.06 g/cm3)

Color

Colorless to light yellow

SMILES

O=C(N1CCCCC1CCCOC)OC2=CC=C(C=C2)[N+]([O-])=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Pure form -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 100 mg/mL (310.21 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.1021 mL 15.5106 mL 31.0212 mL
5 mM 0.6204 mL 3.1021 mL 6.2042 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.08 mg/mL (6.45 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.49%

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.1021 mL 15.5106 mL 31.0212 mL 77.5530 mL
5 mM 0.6204 mL 3.1021 mL 6.2042 mL 15.5106 mL
10 mM 0.3102 mL 1.5511 mL 3.1021 mL 7.7553 mL
15 mM 0.2068 mL 1.0340 mL 2.0681 mL 5.1702 mL
20 mM 0.1551 mL 0.7755 mL 1.5511 mL 3.8777 mL
25 mM 0.1241 mL 0.6204 mL 1.2408 mL 3.1021 mL
30 mM 0.1034 mL 0.5170 mL 1.0340 mL 2.5851 mL
40 mM 0.0776 mL 0.3878 mL 0.7755 mL 1.9388 mL
50 mM 0.0620 mL 0.3102 mL 0.6204 mL 1.5511 mL
60 mM 0.0517 mL 0.2585 mL 0.5170 mL 1.2926 mL
80 mM 0.0388 mL 0.1939 mL 0.3878 mL 0.9694 mL
100 mM 0.0310 mL 0.1551 mL 0.3102 mL 0.7755 mL
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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WWL229
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