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FIASMA

Functional inhibitors of acid sphingomyelinase, or FIASMA, is a large group of pharmacological compounds inhibiting the enzyme acid sphingomyelinase. This enzyme is mainly located within the lysosome, where it cleaves sphingomyelin to ceramide and sphingosine, the latter of which is then phosphorylated to sphingosine-1-phosphate. These metabolites, and subsequent inhibition of the enzyme, influence the balance between cell death (apoptosis) and cell growth (proliferation). A lack of regulation of this sensitive equilibrium can lead to serious clinical consequences.

Mechanism of action of FIASMAs
FIASMAs inhibit the ASM via an indirect, functional mechanism. They insert into the inner leaf of the lysosomal membrane and subsequently cause membrane-associated enzymes, such as ASM, to detach. Upon detachment from the membrane, these enzymes are cleaved and degraded within lysosomes. Inhibition of ASM by certain drugs has been known about for a long time, but systematic studies which characterize the pharmacological group of FIASMAs are relatively recent. ASM is not completely inhibited by FIASMAs == Properties of FIASMAs ==
Properties of FIASMAs
FIASMAs are structurally diverse, but have common physicochemical properties. All FIASMAs identified so far share a basic nitrogen atom • In cystic fibrosis, accumulation of ceramide can be lowered using FIASMAs such as amitriptyline. == Known drugs acting as FIASMAs ==
Known drugs acting as FIASMAs
Cell culture-based experiments identified the listed compounds as FIASMAs (antidepressants are in boldface). These experiments used the human cell line H4. The ASM activity was measured using a radiolabel assay. In case of absent experimental data a chemoinformatic prediction system has been proposed, which enables identification of FIASMAs based on molecular properties. == References ==
Source: Wikipedia ↗
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