GW 4869

A cell-permeable, symmetrical dihydroimidazolo-amide compound that acts as a potent, specific, non-competitive inhibitor of N-SMase (neutral sphingomyelinase) [IC50 = ~ 1 μM, rat brain; Km for sphingomyelin ~13 μM]. Does not inhibit human A-SMase (acid sphingomyelinase) even at 150 μM. Weakly inhibits the activities of bovine protein phosphatase 2A and mammalian lyso-PAF PLC, while no inhibition is observed for bacterial phosphatidylcholine-specific PLC. Reported to offer complete protection against TNF-α or diamine-induced cell death in MCF7 breast Y cells at 20 μM. Does not modify the intracellular glutathione levels or interfere with TNF-α or diamine-mediated signaling effects.