Table 1.
IC50 or Ki values for sp2-iminosugars 1–8 human lysosomal hexosaminidases and recombinant human O-GlcNAcase.a
| Human enzymes |
|||
|---|---|---|---|
| IC50 (µM) |
Ki (µM) |
||
| Compound | Total Hexb | HexAb pH 7/pH 5 | OGA |
| DGJNAc thioureas | |||
| 1 | >100 | 4.7/33.7 | >100 |
| 2 | >100 | >100/>100 | >100 |
| 3 | >100 | >100/>100 | >100 |
| 4 | 10.9 | 0.91/9.4 | >100 |
| DGJNAc isothioureas | |||
| 5 | 2.6 | 0.99/9.8 | >100 |
| 6 | 1.3 | 0.58/6.4 | >100 |
| 7 | 2.2 | 0.66/6.9 | 25 |
| 8 | 0.33 | 0.41/3.9 | >100 |
aIC50 and Ki data are the mean of three independent determinations; errors are in the range of 5–10% and are omitted for clarity. Inhibition was competitive in all cases. No inhibition was observed for any compound at 200 μM on lysosomal α-glucosidase, α- and β-galactosidases and α- and β-mannosidases in cell lysates.
bDetermined in human fibroblast lysates.