Isofagomine (D-tartrate) is a competitive inhibitor of human lysosomal β-glucosidase (Ki = 0.016-0.025 ?M; IC50 = 0.06 ?M).1 By interacting with the catalytic pocket of β-glucosidase it acts as a chemical chaperone that increases the amount of β-glucosidase by stabilizing and/or promoting the folding of the enzyme.2 Isofagomine (D-tartrate) has been shown to increase lysosomal β-glucosidase activity by 2- to 3-fold in mutant N370S Gaucher fibroblasts.1 This compound has been studied in the context of Gaucher disease, a lysosomal storage disorder resulting from substantial deficiency of β-glucosidase and recently identified as a parkinsonism risk factor.2
1.Kuriyama, C., Kamiyama, O., Ikeda, K., et al.In vitro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell culturesBioorg. Med. Chem.16(15)7330-7336(2008)
2.Witte, M.D., Kallemeijn, W.W., Aten, J., et al.Ultrasensitive in situ visualization of active glucocerebrosidase moleculesNat. Chem. Biol.6(12)907-913(2010)
