N-Nonyldeoxynojirimycin

N-Nonyldeoxynojirimycin (NN-DNJ) is an inhibitor of acid α-glucosidase and α-1,6-glucosidase (IC₅₀s = 0.42 and 8.4 μM, respectively).¹ NN-DNJ (250 mg/kg per day) increases hepatic glycogen levels in fasted mice and gastrocnemius muscle glycogen levels in both fasted and fed mice. It is a chemical chaperone of β-glucosidase that increases activity by 1.65-fold in patient-derived fibroblasts homozygous for the N370S Gaucher disease mutation when added to the culture medium at a concentration of 5 μM, but inhibits β-glucosidase activity at concentrations greater than 60 μM.² NN-DNJ inhibits viral replication in BHK-21 cells infected with Japanese encephalitis virus (JEV) or dengue virus serotype 2 (DEN-2) and has protective effects in a mouse model of lethal JEV challenge when administered at a dose of 200 mg/kg per day.³

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1. Andersson, U., Reinkensmeier, G., Butters, T.D., et al. Inhibition of glycogen breakdown by imino sugars in vitro and in vivo. Biochem. Pharmacol. 67(4), 697-705 (2004).

2. Sawkar, A.R., Cheng, W.-C., Beutler, E., et al. Chemical chaperones increase the cellular activity of N370S β-glucosidase: A therapeutic strategy for Gaucher disease. Proc. Natl. Acad. Sci. USA 99(24), 15428-15433 (2002).

3. Wu, S.-F., Lee, C.-J., Liao, C.-L., et al. Antiviral effects of an iminosugar derivative on flavivirus infections. J. Virol. 76(8), 3596-3604 (2002).