Development of novel ASM inhibitors and their application to ex vivo and in vivo lung edema models

We have identified a group of potent and very selective ASM (acid sphingomyelinase) inhibitors. The compounds efficiently suppress dexamethasone-induced cell death in vitro and suppress PAF-induced permeability edema in isolated perfused rat lungs. Non-cardiogenic lung edema is a hallmark of acute lung injury (ALI). It remains to be clarified, whether an intraperitoneal or intravenous administration of the ASM inhibitors or application as an aerosol will have an effect in vivo.