Afegostat D-Tartrate (D-Isofagomine (D-Tartrate))

Isofagomine (D-tartrate) is a competitive inhibitor of human lysosomal β-glucosidase (K_i = 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)