Biological activities of scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima

Scyphostatin is a specific inhibitor for mammalian neutral magnesium-dependent sphingomyelinase with a fifty percent inhibition concentration (IC50) value of 1.0 mu M. When used to inhibit lysosomal acid sphingomyelinase, an approximately 50-fold greater concentration is required. In human peripheral monocytes, the compound inhibits bacterial lipopolysaccharide (LPS)-induced prostaglandin E-2 production and LPS-induced interleukin-1 beta production with IC50 values of 0.8 mu M and 0.1 mu M, respectively. In rat, p.o. administration of the compound has also been shown to inhibit carrageenin-induced paw edema. Thus, it is hoped that utility of scyphostatin as a pharmacological tool will contribute to our understanding of the role of ceramide in the cellular inflammation process.