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> GW4869 [6823-69-4]

GW4869 [6823-69-4]

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Cat# HY-19363-10mg

Size : 10mg

Brand : MedChemExpress

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GW4869 is a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor with an IC50 of 1 μM. GW4869 is an inhibitor of exosome biogenesis/release.

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

GW4869 Chemical Structure

GW4869 Chemical Structure

CAS No. : 6823-69-4

This product is a controlled substance and not for sale in your territory.

Based on 168 publication(s) in Google Scholar

Other Forms of GW4869:

  • GW4869-13C4 Get quote

    GW4869 purchased from MedChemExpress. Usage Cited in: Protein Cell. 21 September 2022.

    The TAZ protein level in PCDH and NDFIP1-OE SPC-A1 and A549 cells with or without GW4869 (5 μM; 24 h).

    GW4869 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2022 Aug 1;13(1):4461.  [Abstract]

    Immunoblot analysis of TβRII in whole cells lysate and EVs from MDA-MB-231 cells with GW4869 (10 μM) treatment for 48 h. Pre-treatment of cells with GW4869, which inhibits the release of extracellular vesicles, also sharply reduced the TβRII levels in the TEVs

    GW4869 purchased from MedChemExpress. Usage Cited in: Theranostics. 2022 Sep 6;12(15):6527-6547.  [Abstract]

    The hEECs are pre-treated with 0.1% DMSO or 1 µM GW4869 for 24 h, and then co-cultured with isolated endometrial NK cells for another 24 h, in vitro.

    GW4869 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2022 Apr 20;13(4):382.  [Abstract]

    Western blotting is used to detect TIMP2 expression in Caki-1 cells and 786-O cells after adding GW4869 (5 μM) to the coculture system.

    GW4869 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2022 Mar 26;13(3):271.  [Abstract]

    WB analysis of CD63 and CD81 in exosomes extracted from MSC-conditioned medium and GW4869 (10 µM) pretreated MSC-conditioned medium.

    GW4869 purchased from MedChemExpress. Usage Cited in: Adv Mater. 2021 Dec;33(49):e2103471.  [Abstract]

    Whole cells lysate and EVs derived from Vero-E6 cells treated with control DMSO or GW4869 (10 μM) for 48 h. Pre‐treatment of cells with GW4869, which inhibits the release of extracellular vesicles, also reduced the ACE2 levels in EVs.

    GW4869 purchased from MedChemExpress. Usage Cited in: J Extracell Vesicles. 2021 Feb;10(4):e12068.  [Abstract]

    Representative actin ring and TRAP staining images of BMMs cultured with PC3‐CM depleted EVs using ultracentrifugation or GW4869 (10 μM; 6 h).

    GW4869 purchased from MedChemExpress. Usage Cited in: Biomaterials. 2021 Dec;279:121223.

    The results also show higher expression of tooth development-related proteins (GLI2, GLI3, DLX1, BMP-2, BMP-4), dentinogenesis-related proteins (DSPP, DMP-4) and cementogenesis-related proteins (CAP, CEMP) in the DA-Exo and GW4869+DA-Exo groups than in the GW4869 (20 μM; 24 h) and hDPSC groups.

    GW4869 purchased from MedChemExpress. Usage Cited in: Engineering. 19 October 2021.

    In SNU-449 cells, GW4869 (20 μM; 24 h) into the co-culture system and observed that the Cy3-fluorescence of the recipient cells is dramatically weakened.

    GW4869 purchased from MedChemExpress. Usage Cited in: Cell Rep. 2021 Jan 5;34(1):108576.  [Abstract]

    M1 macrophages are treated with bmiR-29-Exos with or without 10 μM GW4869 for 48 h; then, relative miR-29a expression in macrophages is determined by qPCR.

    GW4869 purchased from MedChemExpress. Usage Cited in: Mol Ther-Nucl Acids. 2021 Apr 24;24:923-938.  [Abstract]

    The diameter of myotubes and the MHC protein expression of the GW4869-treated C26 group were higher than the control C26 group.

    GW4869 purchased from MedChemExpress. Usage Cited in: Mol Ther-Nucl Acids. 2021 Apr 24;24:923-938.  [Abstract]

    The pro-atrophy ability of C26 tumor medium is inhibited by GW4869.

    GW4869 purchased from MedChemExpress. Usage Cited in: Stem Cell Res Ther. 2020 Jan 23;11(1):37.  [Abstract]

    Exos-IL6 are added to macrophages to detect inflammatory cytokines, chemokines, and growth factors in cell culture media. GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; MIP-1, macrophage inflammatory protein-1; IP-10, interferon-inducible protein-10; MDC, macrophage-derived chemokine; MCP-1, monocyte chemoattractant protein-1; TNF-ɑ, tumor necrosis factor.

    GW4869 purchased from MedChemExpress. Usage Cited in: Int J Oncol. 2019 May;54(5):1567-1578.  [Abstract]

    Western blot analysis is used to assess levels of exosome markers in hucMMSCs-exos and GW4869-treated hUCMSCs-CM.

    GW4869 purchased from MedChemExpress. Usage Cited in: Int J Oncol. 2019 May;54(5):1567-1578.  [Abstract]

    LSCC cell AMC-HN-8 is treated with 20 μM GW4869 compared with 0.5% DMSO. 20 μM GW4869 can significantly alter the levels of miR-1246 within the LSCC cells and sEV.

    View All Phospholipase Isoform Specific Products:

    View All Isoforms
    Phospholipase A PLD Phospholipase C
    Description

    GW4869 is a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor with an IC50 of 1 μM. GW4869 is an inhibitor of exosome biogenesis/release[1][2][3][4].

    IC50 & Target

    IC50: 1 μM (neutral sphingomyelinase)[1]
    In Vitro

    GW4869 (10 μM) partially inhibits TNF-induced sphingomyelin (SM) hydrolysis, and 20 μM of the compound is protected completely from the loss of SM. The addition of 10-20 μM GW4869 completely inhibits the initial accumulation of ceramide, whereas this effect is partially lost at later time points (24 h). The action of GW4869 occurs downstream of the drop in glutathione. GW4869 is able, in a dose-dependent manner, to significantly protect from cell death[1].
    GW4869 (10 or 20 μM) inhibits both exosome release and pro-inflammatory cytokine production in macrophages. GW4869 inhibits the ceramide-mediated inward budding of multivesicular bodies (MVBs) and release of mature exosomes from MVBs[2].
    GW4869 also could reverse the inhibition of CCN2 3’-UTR activity by miR-214-enriched exosomes in hepatic stellate cells[3].
    Solution Attention: GW4869 is routinely stored at 80 °C as a stock suspension in DMSO.

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

    GW4869 Related Antibodies

    Cell Viability Assay[1]

    Cell Line: MCF7 human breast cancer cells.
    Concentration: 10-20 μM.
    Incubation Time: 30 min (then treated with TNF (3 nM) followed).
    Result: Significantly inhibited TNF-induced SM hydrolysis, whereas 20 μM of the compound protected completely from the loss of SM.

    Cell Viability Assay[2]

    Cell Line: Fresh RAW264.7 macrophages.
    Concentration: 10 or 20 μM.
    Incubation Time: 2 hours (then treated with 1 μg/mL LPS incubation).
    Result: LPS-triggered exosome generation was remarkably attenuated in macrophages upon pre-treatment of macrophages with 10 μM GW4869, as evidenced by a 22% reduction in the activity of AChE. Such attenuation was further enhanced by treatment with the dose of 20 μM.
    In Vivo

    GW4869 (2.5 μg/g, i.p.) causes inhibition of exosome release blocks LPS-stimulated pro-inflammatory cytokine production and cardiac inflammation in mice. GW4869 mitigates LPS-caused myocardial dysfunction and improves survival in mice[2].
    GW4869 (2.5 μg/g, i.p.) blocks the production of pro-inflammatory cytokines and cardiac inflammation in CLP mice[2].

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

    Animal Model: 10-12 weeks old Male wild-type C57BL/6 mice (Endotoxin-Challenged Mice)[2].
    Dosage: 2.5 μg/g.
    Administration: I.P. once (1 h later, followed by an i.p. injection of LPS (2.5 μg/g, 100 μL)).
    Result: Significantly decreased exosome levels by 37% in sera, compared to levels collected from control mice. At 12 h after LPS injection, the levels of circulating exosomes were increased significantly compared to PBS-controls, as evidenced by a 1.7-fold elevation in the AChE activity.
    Animal Model: 10-12 weeks old Male wild-type C57BL/6 mice (CLP Polymicrobial Sepsis Model)[2].
    Dosage: 2.5 μg/g.
    Administration: I.P. once (before sham or CLP surgery).
    Result: Decreased exosome concentration by 33% compared to mice injected with PBS in sham-surgery controls.
    CLP-stimulated exosome release was significantly inhibited by pre-treatment of CLP mice compared to CLP mice pre-treated with PBS.
    Molecular Weight

    577.50

    Formula

    C30H30Cl2N6O2
    CAS No.

    6823-69-4
    Appearance

    Solid

    Color

    Light yellow to yellow

    SMILES

    O=C(NC1=CC=C(C2=NCCN2)C=C1)/C=C/C3=CC=C(/C=C/C(NC4=CC=C(C5=NCCN5)C=C4)=O)C=C3.02Cl.02Cl
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage

    4°C, sealed storage, away from moisture

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    Solvent & Solubility
    In Vitro: 

    DMSO : 2 mg/mL (3.46 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    H2O : < 0.1 mg/mL (insoluble)

    *GW4869 is usually formulated as a suspension.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.7316 mL 8.6580 mL 17.3160 mL
    5 mM --- --- ---
    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 (sealed storage, away from moisture). 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

    Concentration (start)

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    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.
    Calculation results:
    Working solution concentration: mg/mL
    Purity & Documentation

    Purity: 98.86%

    COA (246 KB) HNMR (298 KB) LCMS (94 KB)

    Handling Instructions (2659 KB)
    References

    • [1]. Luberto C, et al. Inhibition of tumor necrosis factor-induced cell death in MCF7 by a novel inhibitor of neutralsphingomyelinase. J Biol Chem. 2002 Oct 25;277(43):41128-39.  [Content Brief]

      [2]. Essandoh K, et al. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochim Biophys Acta. 2015 Nov;1852(11):2362-71.  [Content Brief]

      [3]. Chen L, et al. Integrins and heparan sulfate proteoglycans on hepatic stellate cells (HSC) are novel receptors for HSC-derived exosomes. FEBS Lett. 2016 Dec;590(23):4263-4274.  [Content Brief]

      [4]. Nakamura H, et al. Sphingomyelin Regulates the Activity of Secretory Phospholipase A2 in the Plasma Membrane. J Cell Biochem. 2015 Sep;116(9):1898-907.  [Content Brief]

    • [1]. Luberto C, et al. Inhibition of tumor necrosis factor-induced cell death in MCF7 by a novel inhibitor of neutralsphingomyelinase. J Biol Chem. 2002 Oct 25;277(43):41128-39.

      [2]. Essandoh K, et al. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochim Biophys Acta. 2015 Nov;1852(11):2362-71.

      [3]. Chen L, et al. Integrins and heparan sulfate proteoglycans on hepatic stellate cells (HSC) are novel receptors for HSC-derived exosomes. FEBS Lett. 2016 Dec;590(23):4263-4274.

      [4]. Nakamura H, et al. Sphingomyelin Regulates the Activity of Secretory Phospholipase A2 in the Plasma Membrane. J Cell Biochem. 2015 Sep;116(9):1898-907.

    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 (sealed storage, away from moisture). 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 1.7316 mL 8.6580 mL 17.3160 mL 43.2900 mL
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    GW4869 Related Classifications

    • Metabolic Enzyme/Protease
    • Phospholipase
    Help & FAQs

    Keywords:

    GW48696823-69-4GW 4869GW-4869PhospholipaseInhibitorinhibitorinhibit

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