AMP-Deoxynojirimycin

AMP-Deoxynojirimycin (AMP-dNM) is a hydrophobic derivative of dNM that potently inhibits β-glucosidase 2 (BGD, IC₅₀ = 0.3 nM), less potently antagonizes glucosylceramide synthase (GCS, IC₅₀ = 25 nM), and only poorly inhibits other GCase isoforms. The lipid messenger ceramide is converted to glucosylceramide by GCS. In the reverse direction, BGD cleaves the glucosyl moiety from glucosylceramide, liberating ceramide, which can be converted into sphingomyelin. AMP-dNM has been shown to induce sterol regulatory element-binding protein-regulated gene expression and cholesterol synthesis in Hep-G2 cells, strongly suppress inflammation in a murine model of hapten-induced colitis, and enhance insulin sensitivity in murine and rat models of insulin resistance.