Functional inhibitors of acid sphingomyelinase (FIASMAs).

Sphingolipids are not only structural components of biological membranes, but also play an important role in cellular signalling and, thus, are involved in cell proliferation and differentiation but also stress and cell death. It is therefore of great clinical relevance to define inhibitors of the enzymes involved in sphingolipid metabolism. Here, we describe the state of the art of functional inhibitors of the acid sphingomyelinase. The acid sphingomyelinase converts sphingomyelin to ceramide, a compound often involved in cell stress. We describe the structural and physicochemical properties, the distribution, the pharmacokinetics, the pharmocodynamics and the clinical use of direct and functional inhibitors of the acid sphingomyelinase.