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GW4869 

Cat. No.: HY-19363 Purity: 96.35%
Handling Instructions

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

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

GW4869 Chemical Structure

GW4869 Chemical Structure

CAS No. : 6823-69-4

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2 mg USD 90 In-stock
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Description

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

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[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 1.5 mM stock suspension in DMSO (Me2SO). Right before use, the suspension is solubilized by the addition of 5% methane sulfonic acid (MSA) (2.5 μl of 5% MSA in sterile double-distilled H2O are added to 50 μL of GW4869 stock suspension)[1]. GW4869 is routinely stored at -30 °C as a 1.5 mM stock suspension in DMSO. Immediately before use, this suspension is solubilized by the addition of 0.25% methane sulfonic acid (2.5 mL of 5% methane sulfonic acid in sterile distilled H2O is added to 47.5 mL of GW4869 stock solution). The suspension is mixed and heated at 37 °C until clear[4].

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.) caused 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].

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 (25 μg/g, 100μL)).
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.
Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

H2O : < 0.1 mg/mL (insoluble)

DMSO : 0.044 mg/mL (0.08 mM; Need ultrasonic and warming)

References
Molecular Weight

577.50

Formula

C₃₀H₃₀Cl₂N₆O₂

CAS No.

6823-69-4

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.[H]Cl.[H]Cl

Shipping

Room temperature in continental US; may vary elsewhere

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Cat. No.: HY-19363