Miglustat exhibits a broad range of bioactivities, characterized by its inhibitory action against various glycosidases and enzymes involved in carbohydrate metabolism and glucosylceramide synthesis. Specifically, it inhibits alpha-glucosidases such as those found in rat intestinal brush border membranes, with notable IC50 values for maltase (2100 nM), sucrase (58000 nM), and isomaltase (2700 nM). It also inhibits lysosomal alpha-glucosidase, Golgi alpha-mannosidase II, and other related enzymes in rat liver, with competitive inhibition noted for endoplasmic reticulum alpha-glucosidase II and Golgi alpha-mannosidase II.
In mice, Miglustat influences glycosphingolipid levels and demonstrates an inhibitory effect on glucosylceramide synthase (IC50 = 50000 nM) and glucosylceramidase with an IC50 of 140 nM. It shows varying inhibitory effects on maltase, lactase, and sucrase, and has shown potential antiviral activities, including inhibition of HIV-1 induced cytopathogenicity in MT-4 and MOLT-4 cells, and activity against SARS-CoV-2.
In human cell studies, Miglustat inhibits beta-glucocerebrosidase and activates beta-glucocerebrosidase mutants, suggesting potential therapeutic implications for Gaucher disease. The compound shows limited Hepatic side effects, with a Drug-Induced Liver Injury (DILI) severity class of 0.0, indicating no significant concerns for liver toxicity in the tested settings. Additionally, it has shown stability in recombinant human lysosomal alpha-glucosidase, which is beneficial for enzyme replacement therapies.
The compound demonstrates moderate antiviral activities against Dengue virus and Bovine viral diarrhea virus with an EC50 of 100000 nM for both, and has also shown antifungal activity and anti-inflammatory effects in human cells. Despite these bioactivities, Miglustat exhibits no significant inhibition or binding affinity towards some cellular components and receptors, suggesting that its inhibitory actions are selective and context-dependent..
Note: Summary generated by AI. Data source: ChEMBL 