GW 4869

Biological Activity

GW 4869 is a selective neutral sphingomyelin phosphodiesterase (N-SMase) inhibitor (IC₅₀ = 1 μM). Exhibits selectivity for neutral sphingomyelinase over acid sphingomyelinase (a-SMase) at concentrations up to 150 μM as well as B. cereus PC-PLC, human lyso-PAF PLC, and bovine PP2A at 10 μM. Blocks exosome biogenesis. Inhibits TNF-α-induced sphingomyelin hydrolysis and TNF-α-induced cell death in MCF-7 cells. Reverses hypoxia-induced pulmonary vasoconstriction in rats. Neuroprotective.

Technical Data

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Background References

1. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction.
   Essandoh et al.
   Biochim.Biophys.Acta, 2015;1852:2362
2. Inhibition of neutral sphingomyelinase-2 perturbs brain sphingolipid balance and spatial memory in mice.
   Tabatadze et al.
   J.Neurosci.Res., 2010;88:2940
3. Cambinol, a novel inhibitor of neutral sphingomyelinase 2 shows neuroprotective properties.
   Figuera-Losada et al.
   PLoS One, 2015;10:e0124481
4. NSMase2 (type 2-neutral sphingomyelinase) deficiency or inhibition by GW4869 reduces inflammation and atherosclerosis in apoe -/- mice.
   Lallemand et al.
   Arterioscler.Thromb.Vasc.Biol., 2018;38:1479

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