AMP-Deoxynojirimycin

The lipid messenger ceramide is converted to glucosylceramide by glucosylceramide synthase (GCS). In the reverse direction, non-lysosomal glucosylceramidase (GCase), also known as β-glucosidase 2 (BGD), cleaves the glucosyl moiety from glucosylceramide, liberating ceramide, which can be converted into sphingomyelin. AMP-deoxynojirimycin (AMP-dNM) is a hydrophobic derivative of dNM. It potently inhibits BGD (IC50 = 0.3 nM), less potently antagonizes GCS (IC50 = 25 nM), but only poorly inhibits other GCase isoforms. AMP-dNM has been shown to strongly suppress inflammation in a murine model of hapten-induced colitis, enhance insulin sensitivity in murine and rat models of insulin resistance, and induce sterol regulatory element-binding protein-regulated gene expression and cholesterol synthesis in HepG2 cells.