GW4869GW4869
MedChemExpress (MCE)
HY-19363
6823-69-4
98.86%
4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months
-20°C, 1 month (sealed storage, away from moisture)
Room temperature in continental US
may vary elsewhere.
GW4869 is a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor with an IC50 of 1 μM. GW4869 is an inhibitor of exosome biogenesis/release.
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.
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].
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. 0 --> GW4869 Related Antibodies Cell Viability Assay[1] Cell Line: MCF7 human breast cancer cells.
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[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]