GW4869

GW4869 (dihydrochloride hydrate) is a cell permeable, selective inhibitor of N-SMase (neutral sphingomyelinase). GW4869 functions as an inhibitor, via a non-competitve manner. N-SMases are important in the metabolism of sphingomyelin producing ceramide and phosphocholine, which are important in cell signaling and regulation. Studies indicate that GW4869 can inhibit the activation of N-SMase by TNF-α in MC7 cells. As a result of this inhibition cell death and growth suppression are inhibited. Although GW4869 does not effect polymorphonuclear neutrophil (PMN) motility, it is useful with formylmethionylleucylphenylanaline (FMLP), since it inhibits PMN aggregation towards the chemotaxin.