GW4869

6823-69-4

C30H30Cl2N6O2

DMSO : 0.044 mg/mL (0.08 mM; Need ultrasonic and warming); H2O : < 0.1 mg/mL (insoluble)

Others

GW4869 is a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor) with an IC₅₀ of 1 uM. IC50 & Target: IC50: 1 uM (neutral sphingomyelinase)^[1] In Vitro: GW4869 (10 uM) partially inhibits TNF-induced sphingomyelin (SM) hydrolysis, and 20 uM of the compound is protected completely from the loss of SM. The addition of 10-20 uM 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 uM) 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 ul of 5% MSA in sterile double-distilled H₂O are added to 50 uL 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]. In Vivo: GW4869 (2.5 ug/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 ug/g, i.p.) blocks the production of pro-inflammatory cytokines and cardiac inflammation in CLP mice^[2].