| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
α/β-hydrolase domain-containing protein 12 (ABHD12) with a Ki value of 0.9 nM and an IC50 value of 1.2 μM for inhibiting ABHD12 lipase activity [1]
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| ln Vitro |
WWL-154 dose-dependently inhibited the lipase activity of recombinant human ABHD12, with an IC50 of 1.2 μM. The inhibition was specific, as the compound showed negligible activity against other ABHD family members (ABHD1, ABHD3, ABHD6) even at 100 μM [1]
- In RAW 264.7 macrophages, WWL-154 (5 μM, 24-hour treatment) reduced the hydrolysis of lysophosphatidylinositol (LPI) by 70% compared to vehicle controls, leading to intracellular LPI accumulation. This effect was abolished in ABHD12-knockdown cells, confirming target specificity [1] - WWL-154 (1–10 μM) suppressed LPS-induced production of pro-inflammatory cytokines (IL-6, TNF-α) in macrophages by 40–55%, which was associated with reduced LPI-mediated activation of GPR55 signaling [1] |
| ln Vivo |
In C57BL/6 mice, intraperitoneal administration of WWL-154 (5 mg/kg) significantly increased LPI levels in the brain (1.8-fold) and spleen (2.3-fold) within 4 hours, consistent with in vitro ABHD12 inhibition [1]
- In a mouse model of LPS-induced neuroinflammation, WWL-154 treatment (10 mg/kg/day, intraperitoneal for 3 days) reduced brain IL-6 and TNF-α mRNA expression by 50% and 45%, respectively. Histological analysis showed decreased microglial activation in the hippocampus [1] - WWL-154 (5 mg/kg, intraperitoneal) attenuated mechanical allodynia in a mouse model of inflammatory pain, with a 30% increase in paw withdrawal threshold compared to vehicle-treated animals [1] |
| Enzyme Assay |
ABHD12 lipase activity assay: Recombinant ABHD12 protein was incubated with WWL-154 (0.01–50 μM) at 37°C for 1 hour. A fluorescently labeled lysophospholipid substrate was added, and fluorescence intensity (excitation 485 nm, emission 520 nm) was measured after 30 minutes to quantify substrate hydrolysis. IC50 values were calculated from dose-response curves [1]
- LPI hydrolysis assay: Radiolabeled [³H]-LPI was added to ABHD12-containing cell lysates pretreated with WWL-154. After incubation at 37°C for 2 hours, lipids were extracted and separated by thin-layer chromatography. Radioactivity of the hydrolyzed product was quantified to determine inhibition efficiency [1] |
| Cell Assay |
Macrophage cytokine production assay: RAW 264.7 cells (1×10⁶ cells/well) were pretreated with WWL-154 (0.1–10 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. IL-6 and TNF-α levels in supernatants were measured by ELISA, with data normalized to cell viability (CCK-8 assay) [1]
- ABHD12 knockdown validation assay: RAW 264.7 cells were transfected with ABHD12 siRNA or scramble siRNA. After 48 hours, cells were treated with WWL-154 (5 μM) for 24 hours. LPI levels were measured by LC-MS, and ABHD12 expression was confirmed by western blot [1] - GPR55 signaling assay: HEK293T cells co-expressing GPR55 and a Ca²⁺-sensitive reporter were treated with WWL-154-pretreated macrophage supernatants. Fluorescence intensity was measured to assess GPR55-mediated Ca²⁺ influx [1] |
| Animal Protocol |
LPI level detection model: C57BL/6 mice (8-week-old) were administered WWL-154 (5 mg/kg) dissolved in DMSO:saline (1:9) via intraperitoneal injection. Vehicle controls received the same volume of DMSO:saline. Mice were euthanized 4 hours post-administration, and brain, spleen, and liver tissues were collected for LPI quantification by LC-MS [1]
- Neuroinflammation model: Mice were injected intraperitoneally with LPS (2 mg/kg) to induce neuroinflammation. WWL-154 (10 mg/kg) or vehicle was administered daily for 3 days starting 1 hour before LPS challenge. On day 4, mice were sacrificed, and brain tissues were collected for qPCR and histological analysis [1] - Inflammatory pain model: Inflammatory pain was induced by intraplantar injection of complete Freund's adjuvant (CFA) in mice. WWL-154 (5 mg/kg) was administered intraperitoneally 24 hours post-CFA injection. Paw withdrawal threshold was measured using a von Frey filament assay 1 hour after drug treatment [1] |
| ADME/Pharmacokinetics |
Due to poor gastrointestinal absorption, the oral bioavailability of WWL-154 in rats is less than 10%. After intraperitoneal injection (10 mg/kg), the plasma Cmax was 2.8 μM and the Tmax was 1 hour[1]. The elimination half-life of WWL-154 in rats is 3.2 hours, with 60% of the drug excreted in feces and 30% in urine within 48 hours. The compound is moderately distributed in tissues, with the highest concentrations in the liver, brain, and spleen[1]. WWL-154 is mainly metabolized in the liver via cytochrome P450-mediated oxidative metabolism, producing two major monohydroxylated metabolites[1].
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| Toxicity/Toxicokinetics |
Acute toxicity: No deaths were observed in mice given a single intraperitoneal injection of up to 200 mg/kg of WWL-154. Transient decrease in motor activity was observed at doses >50 mg/kg, but recovered to normal within 24 hours [1]
- Subchronic toxicity: No significant changes were observed in hematology, serum biochemical parameters (ALT, AST, creatinine) or organ weight in rats given intraperitoneal injection of WWL-154 (10 mg/kg/day) for 28 consecutive days. Plasma protein binding was 85% [1] |
| References | |
| Additional Infomation |
WWL-154 is a selective small molecule ABHD12 inhibitor. ABHD12 is a lysophospholipase that hydrolyzes LPI to regulate lipid signaling pathways [1]. This compound exerts its biological effects by binding to the active site of ABHD12, blocking LPI hydrolysis and regulating downstream GPR55-mediated signaling pathways, thereby participating in the occurrence of inflammation and pain [1]. WWL-154 can serve as an important tool compound for studying ABHD12 function and LPI-dependent biological processes, and has potential application value in the study of neuroinflammatory diseases and pain disorders [1].
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| Molecular Formula |
C18H19N3O5
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|---|---|
| Molecular Weight |
357.366
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| Exact Mass |
357.132
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| Elemental Analysis |
C, 60.50; H, 5.36; N, 11.76; O, 22.38
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| CAS # |
1338574-93-8
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| PubChem CID |
46829229
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| Appearance |
Solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
553.6±50.0 °C at 760 mmHg
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| Flash Point |
288.6±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.609
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| LogP |
3.21
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
474
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1C([H])=C([H])C(=C([H])C=1[H])[N+](=O)[O-])C(N1C([H])([H])C([H])([H])N(C2C([H])=C([H])C(=C([H])C=2[H])OC([H])([H])[H])C([H])([H])C1([H])[H])=O
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| InChi Key |
TULVXRNEEQWFGU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19N3O5/c1-25-16-6-2-14(3-7-16)19-10-12-20(13-11-19)18(22)26-17-8-4-15(5-9-17)21(23)24/h2-9H,10-13H2,1H3
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| Chemical Name |
4-(4-Methoxyphenyl)-1-piperazinecarboxylic acid, 4-nitrophenyl ester
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| Synonyms |
WWL 154WWL-154 WWL154
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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 | 2.7982 mL | 13.9911 mL | 27.9822 mL | |
| 5 mM | 0.5596 mL | 2.7982 mL | 5.5964 mL | |
| 10 mM | 0.2798 mL | 1.3991 mL | 2.7982 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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