myriocin

Myriocin ((2S,3R,4R,6E)-2-amino-3,4- dihydroxy-2-(hydroxymethyl)-14-oxo-6-eicosenoic acid, ISP-1, thermozymocidin) is a small-molecule immunosuppressant, isolated from the Mycelia sterilia thermophilic fungus. Myriocin inhibits serine palmitoyltransferase (SPT) at picomolar concentrations blocking synthesis of ceramide, a precursor of sphingomyelin (SM) and glycosphingolipids. Inhibition of hepatic serine palmitoyl transferase reduces plasma sphingomyelin levels in the absence of changes in cholesterol or triglyceride (TG) concentration and this leads to a reduction of atherosclerosis. In preclinical studies, Myriocin treated mice shows significant reductions in both plasma SM and Glycosphingolipids (GSL) concentration. Moreover, SM and GSL concentrations were significantly correlated, indicating that SPT inhibition suppresses the synthesis of both these sphingolipids concomitantly. The inhibition of atherosclerosis induced by myriocin was not associated with changes in plasma cholesterol or TG concentrations or lipoprotein profiles. — NCATS