Table 2.
Kinetic parameters of the inhibition of HDAC6 by 1
| HDAC6 forms | Parameters | 1 |
|---|---|---|
| Human HDAC6 | IC50, nM | 7.7 ± 0.3 |
| 8.1 ± 0.3a | ||
| konapp, M−1 min−1 (×105)b | 9.6 ± 0.3 | |
| 9.1 ± 0.3a | ||
| koffapp, min−1 (×10−3)b | 4.6 ± 2.3 | |
| 6.7 ± 1.9a | ||
| koffapp, min−1 (×10−3)c | 3.3 ± 0.2 | |
| Kiapp, nMd | 4.8 ± 2.4 | |
| 6.9 ± 1.9a | ||
| Mode of inhibition | Slow-on/slow-off | |
| zHDAC6-CD2 WT | IC50, nM | 7.8 ± 0.4 |
| konapp, M−1 min−1 (×105)b | 15.1 ± 0.1 | |
| koffapp, min−1 (×10−3)b | 12.8 ± 1.1 | |
| koffapp, min−1 (×10−3)c | 9.6 ± 1.1 | |
| Kiapp, nMd | 8.5 ± 0.7 | |
| Mode of inhibition | Slow-on/slow-off | |
| zHDAC6-CD2 Y745F | IC50, nM | 15.1 ± 0.9 |
| konapp, M−1 min−1 (×105)b | ∼1010d | |
| koffapp, min−1 (×10−3)c | 92.7 ± 3.2 | |
| Mode of inhibition | Fast-on/slow-off |
Parameters determined in D2O.
Calculated from kobs plot, Kiapp = koffapp/konapp.
koffapp values from jump-dilution assay.
Parameter estimated from koffapp/Kiapp ratio.