Table 1.
Percent inhibition of hAdK activity for all 14 inhibitors, relative to uninhibited activity, at concentrations of 50 μM, 20 μM, 500 nM, and 100 nM and the derived IC50 values.
| Inhibition at concentration indicated,a mean % ± SEM | IC50 | ||||
|---|---|---|---|---|---|
| Compound | 50 μM | 20 μM | 500 nM | 100 nM | (μM) + SEM |
| Control | 0 | 0 | 0 | 0 | ND |
| 1a, 5-IT | 88.3 ± 0.3 | 88.3 ± 0.3 | 44.4 ± 0.8 | 21.5 ± 0.9 | 0.82 ± 0.03 |
| 2 | 88.4 ± 0.3 | 88.3 ± 0.3 | 86.7 ± 0.2 | 59.0 ± 1.3 | 0.048 ± 0.001 |
| (S)-Methanocarba nucleosides | |||||
| 28 | 76.5 ± 0.9 | 68.9 ± 0.8 | 15.6 ± 1.4 | 6.6 ± 1.7 | 6.01 ± 0.18 |
| 30 | 58.2 ± 1.7 | 41.7 ± 0.9 | 8.8 ± 0.9 | 1.1 ± 2.1 | ND |
| 32 | 85.1 ± 0.6 | 80.9 ± 0.2 | 20.7 ± 0.8 | 2.9 ± 1.9 | 3.34 ± 0.19 |
| 34 | 88.3 ± 0.4 | 88.1 ± 0.3 | 82.2 ± 0.4 | 41.0 ± 1.2 | 0.114 ± 0.002 |
| 38a | 88.1 ± 1.5 | 88.4 ± 0.4 | 86.0 ± 0.3 | 49.7 ± 1.0 | 0.088 ± 0.003 |
| 38b | 86.9 ± 0.3 | 88.0 ± 0.3 | 85.2 ± 0.3 | 39.0 ± 1.2 | 0.110 ± 0.003 |
| 38c | 78.4 ± 0.7 | 88.6 ± 0.2 | 87.3 ± 0.3 | 35.6 ± 1.3 | 0.115 ± 0.005 |
| 43 | 80.5 ± 0.8 | 75.1 ± 0.5 | 6.8 ± 0.7 | 6.1 ± 3.8 | 5.38 ± 0.10 |
| 45 | 50.9 ± 1.1 | 36.0 ± 1.4 | −2.0 ± 2.7 | 8.4 ± 1.9 | ND |
| 49 | 60.4 ± 0.8 | 44.9 ± 0.7 | −1.3 ± 1.7 | −5.8 ± 2.0 | ND |
| (N)-Methanocarba nucleosides | |||||
| 55 | 85.4 ± 0.5 | 88.0 ± 0.2 | 82.3 ± 0.5 | 35.5 ± 1.4 | 0.14 ± 0.01 |
| 57 | 82.5 ± 0.3 | 79.5 ± 0.4 | 23.6 ± 1.1 | 12.3 ± 0.4 | 2.24 ± 0.04 |
a
based on slope of the linear portion (0 – 40 min interval) of the activity plot of hAdK, compared to control with DMSO vehicle. ND, not determined.