Product Overview:
Neutral sphingomyelinases mediate the release of ceramide from sphingomyelin in cellular membranes and can be activated by certain stresses. Ceramide can act as a signaling molecule in its own right, or it can be further processed to generate sphingosine (and sphingosine-1-phosphate). GW 4869 is an inhibitor of neutral sphingomyelinase (IC50 = 1 μM).{17163} It is selective for neutral sphingomyelinase over acid sphingomyelinase at concentrations up to 150 μM as well as B. cereus PC-PLC, human lyso-PAF PLC, and bovine PP2A at 10 μM. GW 4869 inhibits TNF-α-induced sphingomyelin hydrolysis by 100% when used at a concentration of 20 μM and TNF-α-induced cell death in MCF-7 cells.{17163,17164} It also reduces the inhibitory effects of oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphatidylcholine (OxPAPC) and the 5-keto-6-octendioic acid ester of 2-lysophosphatidylethanolamine (KOdiA-PE) on LPS-induction of IL-8 in human aortic endothelial cells.{17165} In vivo, GW 4869 (1 mg/kg) reverses hypoxia-induced pulmonary vasoconstriction in rats.{17166}