Miglustat HCl (OGT-918; NB-DNJ; Zavesca)

Description: Miglustat HCl (OGT-918; NB-DNJ; Zavesca) is an FDA approved drug used to treat Type I Gaucher disease (GD1). It inhibits the enzyme glucosylceramide synthase, an essential enzyme for the synthesis of most glycosphingolipids. It is only used for patients who cannot be treated with enzyme replacement therapy with imiglucerase. Miglustat is an imino sugar, a synthetic analogue of D-glucose and a white to off-white crystalline solid that has a bitter taste. The primary pharmacological activity of miglustat is inhibition of the enzyme glucosylceramide synthase, catalyzing the first step in the biosynthesis of glycosphingolipids (GSL), i.e., the formation of glucosylceramide (GlcCer). Reduced formation of GlcCer will lead to decreased biosynthesis of more complex GSL. This therapeutic principle, called substrate reduction therapy (SRT), may be useful in disorders of intracellular (predominantly lysosomal) accumulation of GSL either due to their deficient breakdown or intracellular transport/trafficking. Miglustat exhibits a large volume of distribution and has the capacity to access deep organs such as the brain, bone and lung.

References:

1. Abian, O., et al., Therapeutic strategies for Gaucher disease: miglustat (NB-DNJ) as a pharmacological chaperone for glucocerebrosidase and the different thermostability of velaglucerase alfa and imiglucerase. Mol Pharm, 2011. 8(6): p. 2390-7.

2. van Giersbergen, P.L. and J. Dingemanse, Influence of food intake on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase. J Clin Pharmacol, 2007. 47(10): p. 1277-82.

3. Kitatani T, Takahashi S, Ikenoya S. Pharmacological and clinical profiles of miglustat (Brazaves(A)) for the treatment of Niemann-Pick type C disease. Nihon Yakurigaku Zasshi. 2013 Mar; 141(3):160-7. Review. Japanese.

Related CAS #: 72599-27-0 (free base) 210110-90-0 (HCl)