JW480
Based on 1 Customer Validation
JW480 is a selective KIAA1363/AADACL1 inhibitor with oral activity, featuring IC50 values of 12 nM against human KIAA1363, 20 nM against mouse KIAA1363. JW480 blocks lipid deacetylase activity to restrain HAG metabolism and lowers retinyl ester hydrolase function in hepatic stellate cells. JW480 reduces MAGE lipid levels and inhibits migration, invasion, survival and tumor growth of prostate cancer cells. JW480 lowers PKCδ phosphorylation, facilitates HAGP accumulation, diminishes platelet aggregation, dense granule secretion and Ca2+ flux, delays arterial thrombosis and prolongs tail bleeding time in rats. JW480 can be used for the study of prostate cancer and thrombosis.
For research use only. We do not sell to patients.
- Purity : 99.82%
- CAS No.: 1354359-53-7
- Formula: C22H23NO2
- Molecular Weight:333.42
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Storage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
[3]|
PKCδ |
In Vitro
JW480 (0.001-10 μM) potently and selectively inhibits KIAA1363 with an IC50 of 0.02 μM in mouse brain membrane proteomes and an in situ IC50 of 0.006 μM in living PC3 cells, with sustained inhibition[1].
JW480 (0.001-50 μM) potently and selectively inhibits KIAA1363 in PC3 prostate cancer cell proteomes in vitro with an IC50 of 0.012 μM[1].
JW480 (1 μM; 48 hr) selectively and exclusively inhibits KIAA1363 in situ–treated PC3 prostate cancer cells. It fully abolishes KIAA1363‑dependent 2‑acetyl MAGE hydrolysis and markedly reduces C16:0, C18:0, and C18:1 MAGE lipid levels in both PC3 and DU144 prostate cancer cells[1].
JW480 (1 μM; 48 hr) impairs cell migration and invasion in PC3 prostate cancer cells treated in situ[1].
JW480 (1 μM; 48 hr) impairs cell survival in serum-free media over 4 days in PC3 prostate cancer cells treated in situ[1].
JW480 (10 μM, 1 h) markedly suppresses the in vitro retinyl ester (RE) hydrolase activity of recombinant mouse and human KIAA1363 in Expi293FTM cell lysates by 90% and 86%, respectively, and abolishes RE hydrolase activity across all subcellular fractions of mKIAA1363‑expressing Expi293FTM cells.[2].
JW480 (10 μM; 1 h) reduces in vitro RE hydrolase activity by 20% in whole mouse liver lysates and by 60% in primary mouse HSC lysates, with no effect on primary mouse hepatocyte lysates[2].
JW480 (10 μM; 1 h) potently inhibits in vitro RE hydrolase activity, reducing activity by 80% in human LX-2 HSC lysates and by 92% in primary human HSC lysates[2].
JW480 (10 μM, 8 h) significantly suppresses RE degradation in HSCs, blunting RP breakdown in primary mouse HSCs, blocking RE degradation entirely in human LX‑2 cells, and lifting RP levels by 4‑fold in primary human HSCs.[2].
JW480 elevates HAGP levels in collagen‑stimulated human platelets, inhibits collagen‑induced platelet aggregation (rescued by ADP), and reduces dense granule ATP secretion by 45% in washed human platelets[3].
JW480 (2-10 μM) dose-dependently inhibits collagen-induced PKCδT505 phosphorylation in human platelets, with no effect on PKCθT538 phosphorylation[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:human PC3 prostate cancer cells
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Concentration:1 μM
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Incubation Time:48 hr
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Result:Caused a significant reduction in invaded cells compared to control.
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Cell Line:human PC3 prostate cancer cells
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Concentration:1 μM
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Incubation Time:48 h (treatment), 4 d (culture)
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Result:Caused significant reductions in cell survival at days 1, 2, 3, and 4 compared to control.
In Vivo
JW480 (1-80 mg/kg; i.p.; single dose; 5-80 mg/kg; p.o.; single dose) potently and selectively inhibits brain KIAA1363 in mice via both intraperitoneal and oral routes[1].
JW480 (40 mg/kg; i.v.; single dose over 5 minutes) administered to 3.5 to 5 week-old Sprague Dawley rats significantly delays median time to FeCl3-induced carotid artery occlusion to 14.8 minutes[3].
JW480 (3.5-10 mg/kg; i.v.; single dose over 5 minutes) administered to adult (≥6 months old) Sprague Dawley rats significantly increases median tail bleeding time to 30.0 minutes[3].
JW480 (8-11 mg/kg; i.v.; single dose) administered to adult (>6 months old) Sprague Dawley rats significantly inhibits convulxin-induced circulating platelet aggregation[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C.B17 SCID mice (immune-deficient)[1]
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Dosage:80 mg/kg
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Administration:p.o.; daily; 33 days
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Result:Significantly reduced PC3 tumor xenograft growth compared to vehicle control.
Completely ablated KIAA1363 activity in explanted tumors.
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Animal Model:Mice[1]
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Dosage:1-80 mg/kg (i.p., single dose); 5-80 mg/kg (p.o., single dose); 20 mg/kg (p.o., single dose for time-course analysis)
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Administration:i.p.; single dose; p.o.; single dose
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Result:Achieved complete inhibition of brain KIAA1363 at 5 mg/kg (i.p.) and 20 mg/kg (p.o.) 4 hours post-administration.
Maintained inhibition of brain KIAA1363 for up to 24 hours following a single 20 mg/kg oral dose.
Showed excellent selectivity for KIAA1363 in brain proteomes, with only carboxylesterase ES1 (likely from blood contamination) identified as an off-target.
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Animal Model:Sprague Dawley (SD) (3.5 to 5 weeks old, FeCl3-induced common carotid artery thrombosis model)[3]
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Dosage:40 mg/kg
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Administration:i.v.; single dose over 5 minutes
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Result:Delayed the median time to vessel occlusion (defined as blood flow reaching 25% of baseline) to 14.8 minutes.
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Animal Model:Sprague Dawley (SD) (adult, ≥ 6 months old, tail bleeding assay model)[3]
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Dosage:3.5-10 mg/kg
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Administration:i.v.; single dose over 5 minutes
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Result:Increased median tail bleeding time to 30.0 minutes.
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Animal Model:Sprague Dawley (SD) (adult, > 6 months old)[3]
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Dosage:8-11 mg/kg
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Administration:i.v.; single dose
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Result:Produced a pronounced inhibition of convulxin-induced whole blood platelet aggregation, normalized to vehicle control set to 1.0.
Chemical Information
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CAS No. 1354359-53-7
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Appearance Solid
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Molecular Weight 333.42
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Formula C22H23NO2
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Color White to off-white
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SMILES
O=C(NCCC1=CC2=C(C=CC=C2)C=C1)OC3=C(C(C)C)C=CC=C3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (299.92 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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 (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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 (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (7.50 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
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).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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.
Protocols
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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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Western Blot
Western blotting (WB) is a commonly used experimental method in molecular biology, biochemistry, and immunogenetics for identifying and quantifying target proteins. It combines gel electrophoresis with immunoassay, enabling researchers to analyze protein expression, post-translational modifications, and molecular weight.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Cell migration
Cell migration is a method that plays an important role in wound healing, cell differentiation, embryonic development, etc.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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Cell invasion
Cell invasion is the ability of cells to migrate from one area to another via the extracellular matrix. Cell invasion is the response of normal and cancer cells to chemical and mechanical stimuli. Before migrating to a new region, the extracellular matrix is degraded by proteases within the cell. Cell invasion often occurs during wound repair, vascularization and inflammation, abnormal tissue invasion, and tumor cell metastasis.
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
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Ca2+ Staining Technique
Ca2+ staining is an experimental technique that utilizes specific fluorescent probes (such as Fluo-4 AM, Fura-2, etc.) to qualitatively or quantitatively detect dynamic changes in intracellular Ca2+ concentrations; this is achieved by monitoring the changes in fluorescent signals generated when these probes bind to free intracellular calcium ions. The underlying principle relies primarily on the presence of chelating groups within the probe's molecular structure that possess high affinity for calcium ions.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
Purity & Documentation
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Data Sheet (283 KB)
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SDS (624 KB)
- English - EN (624 KB)
- Français - FR (624 KB)
- Deutsch - DE (624 KB)
- Norwegian - NO (624 KB)
- Español - ES (624 KB)
- Swedish - SV (624 KB)
- Italian - IT (624 KB)
- Korean - KR (624 KB)
- Portuguese - PT (624 KB)
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Handling Instructions (2659 KB)
References
[1]. Chang JW, et al. A potent and selective inhibitor of KIAA1363/AADACL1 that impairs prostate cancer pathogenesis. Chem Biol. 2011;18(4):476-484. [Content Brief]
[2]. Wagner C, et al. KIAA1363 affects retinyl ester turnover in cultured murine and human hepatic stellate cells. J Lipid Res. 2022;63(3):100173. [Content Brief]
[3]. Holly SP, et al. Ether lipid metabolism by AADACL1 regulates platelet function and thrombosis. Blood Adv. 2019;3(22):3818-3828. [Content Brief]
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 (protect from light). 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 | 2.9992 mL | 14.9961 mL | 29.9922 mL | 74.9805 mL |
| 5 mM | 0.5998 mL | 2.9992 mL | 5.9984 mL | 14.9961 mL | |
| 10 mM | 0.2999 mL | 1.4996 mL | 2.9992 mL | 7.4981 mL | |
| 15 mM | 0.1999 mL | 0.9997 mL | 1.9995 mL | 4.9987 mL | |
| 20 mM | 0.1500 mL | 0.7498 mL | 1.4996 mL | 3.7490 mL | |
| 25 mM | 0.1200 mL | 0.5998 mL | 1.1997 mL | 2.9992 mL | |
| 30 mM | 0.1000 mL | 0.4999 mL | 0.9997 mL | 2.4994 mL | |
| 40 mM | 0.0750 mL | 0.3749 mL | 0.7498 mL | 1.8745 mL | |
| 50 mM | 0.0600 mL | 0.2999 mL | 0.5998 mL | 1.4996 mL | |
| 60 mM | 0.0500 mL | 0.2499 mL | 0.4999 mL | 1.2497 mL | |
| 80 mM | 0.0375 mL | 0.1875 mL | 0.3749 mL | 0.9373 mL | |
| 100 mM | 0.0300 mL | 0.1500 mL | 0.2999 mL | 0.7498 mL |
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