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| 25mg |
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| Targets |
JW-480 targets KIAA1363 (also known as AADACL1 or NCEH1), a serine hydrolase enzyme involved in lipid metabolism and cancer progression. KIAA1363 is overexpressed in various cancers and plays a role in tumor cell migration, invasion, and growth. By covalently inhibiting KIAA1363, JW-480 blocks the enzyme's activity, disrupting the KIAA1363-MAGE pathway. This leads to impaired cancer cell migration, invasion, and tumor growth. The compound shows superior selectivity over earlier probes such as AS115, JW148, and WWL38. Its potent and selective inhibition of KIAA1363 makes it a valuable pharmacological probe for investigating cancer biology and developing novel anticancer therapies targeting serine hydrolases.
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| ln Vitro |
In vitro, JW-480 demonstrates potent and selective inhibition of KIAA1363. It has an IC50 of 20 nM in mouse brain membrane proteomes and 6-12 nM in human PC3 prostate cancer cell proteomes. The compound is a covalent inhibitor, forming an irreversible bond with the enzyme's active site serine residue. In cell-based assays, JW-480 impairs migration and invasion of cancer cells. The compound shows superior selectivity for KIAA1363 over other serine hydrolases and unrelated targets. Its activity is concentration-dependent, with effective concentrations ranging from 1 nM to 10 µM. JW-480's potent and selective inhibition makes it a valuable tool for studying the role of KIAA1363 in cancer biology, lipid metabolism, and cell signaling.
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| ln Vivo |
In vivo, JW-480 has been evaluated in preclinical models of prostate cancer. The compound inhibits tumor growth and impairs metastasis in mouse xenograft models. Its in vivo efficacy is consistent with its potent in vitro activity against KIAA1363. Pharmacodynamic studies confirm target engagement, showing reduced KIAA1363 activity in tumor tissues following treatment. JW-480 is typically administered via intraperitoneal injection in preclinical studies. Its ability to inhibit tumor growth and metastasis without significant toxicity makes it a promising candidate for further development as an anticancer therapeutic. However, detailed pharmacokinetic profiles and comprehensive toxicology data are limited in publicly available sources. Further studies are needed to fully characterize its therapeutic potential.
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| Enzyme Assay |
The in vitro KIAA1363 inhibition assay for JW-480 typically uses mouse brain membrane proteomes or human cancer cell proteomes as the enzyme source. The assay is performed in 96-well plates using a fluorogenic substrate specific for serine hydrolases (e.g., fluorophosphonate-rhodamine or a coumarin-based substrate). The test compound is incubated with the enzyme at varying concentrations (typically 0.1 nM to 10 µM) for 30-60 minutes at room temperature. The reaction is initiated by adding the substrate, and fluorescence is measured over time. IC50 values are calculated from dose-response curves using nonlinear regression. For covalent inhibition studies, the compound is pre-incubated with the enzyme before substrate addition to assess time-dependent inhibition. Positive controls (e.g., known serine hydrolase inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, cancer cell lines (e.g., PC3 prostate cancer cells) are treated with JW-480 at concentrations ranging from 0.01 to 10 µM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Cell migration is evaluated using wound-healing or Transwell migration assays. Cell invasion is assessed using Matrigel-coated Transwell inserts. KIAA1363 activity in cell lysates is measured using activity-based protein profiling (ABPP) with a fluorophosphonate probe. For mechanism studies, the effects of the compound on KIAA1363-MAGE pathway signaling are investigated by Western blotting. All experiments include appropriate controls (vehicle, known inhibitors) and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are subcutaneously inoculated with prostate cancer cells (e.g., PC3). When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). JW-480 is administered intraperitoneally at doses ranging from 1 to 50 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for Western blot analysis of KIAA1363 activity, and for immunohistochemistry (Ki67, cleaved caspase-3, CD31). Metastasis is evaluated by examining secondary organs for tumor cell dissemination. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of JW-480 have been partially characterized. Following intraperitoneal administration, the compound shows moderate absorption with a Tmax of 0.5-1 hour. Plasma half-life is estimated to be 2-4 hours. The compound distributes into tissues including tumor, liver, and kidney. Plasma protein binding is moderate to high due to its lipophilic nature (LogP ~4). Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is limited due to first-pass metabolism. The compound's covalent binding to KIAA1363 may result in prolonged target engagement. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of JW-480 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| Additional Infomation |
Carbamic acid, N-[2-(2-naphthyl)ethyl]-,2-(1-methylethyl)phenyl ester, is a member of the naphthalene family of compounds.
JW-480 is a potent and selective covalent inhibitor of the serine hydrolase KIAA1363 (NCEH1), with IC50 values of 20 nM in mouse brain and 6-12 nM in human PC3 cells. It impairs cancer cell migration, invasion, and tumor growth in prostate cancer models, making it a validated probe for the KIAA1363-MAGE pathway. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent for laboratory use only. Its potency and selectivity make it a valuable tool for studying cancer biology, lipid metabolism, and serine hydrolase function. |
| Molecular Formula |
C22H23NO2
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|---|---|
| Molecular Weight |
333.42
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| Exact Mass |
333.172
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| CAS # |
1354359-53-7
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| PubChem CID |
57330099
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
486.2±38.0 °C at 760 mmHg
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| Flash Point |
247.9±26.8 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.605
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| LogP |
5.93
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
422
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C1=CC=CC=C1OC(NCCC2=CC3=CC=CC=C3C=C2)=O)C
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| InChi Key |
PCNJGBMWAZRVEA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23NO2/c1-16(2)20-9-5-6-10-21(20)25-22(24)23-14-13-17-11-12-18-7-3-4-8-19(18)15-17/h3-12,15-16H,13-14H2,1-2H3,(H,23,24)
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| Chemical Name |
(2-propan-2-ylphenyl) N-(2-naphthalen-2-ylethyl)carbamate
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~100 mg/mL (~299.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.50 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9992 mL | 14.9961 mL | 29.9922 mL | |
| 5 mM | 0.5998 mL | 2.9992 mL | 5.9984 mL | |
| 10 mM | 0.2999 mL | 1.4996 mL | 2.9992 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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