Summary /

Comparative data showing probe specificity for target: The selectivity of ML010 was measured in three other hydrolases including α-glucosidase, α-galactosidase, and β-N-acetylglucosaminidase (β-N-acetylhexosaminidase, HEX). Deficiencies in α-glucosidase, α-galactosidase and β-hexosaminidase result in Pompe disease, Fabry disease and Tay-Sachs or Sandhoff disease, respectively, all genetic disorders of lysosomal lipid metabolism like Gaucher disease (Vellodi A, 2005). Substrates of these three enzymes labeled with the blue fluorophore 4-methylumbelliferone were used with a GC enzyme assay using the substrate 4-methylumbelliferyl-β-D-glucopyranoside (4MU-β−Glc) as control. These four enzyme assays were performed in parallel with the 1536-well plates (Urban DJ, 2008). Results showed that ML010 (SID 847960), did not inhibit the activities of α-glucosidase, α-galactosidase, or β-hexosaminidase at concentrations up to 77 μM, demonstrating high selectivity to GC. In contrast, the iminosugar nonyl-DNJ was found to inhibit both GC and α-glucosidase, with IC50 values of 0.103 and 0.050 μM, respectively. The IC50 values of the compounds in the GC enzyme assay using the blue fluorogenic substrate 4MU-β−Glc were like those using fluorogenic substrate Res-β-Glc.