TABLE 4.
Values of dissociation constants kon, koff, and Kd and t1/2 of HCV NS5B NNIs determined by SPR
| Compound and NS5BΔ21 enzyme | Parameter |
|||
|---|---|---|---|---|
| kon (M−1s−1)a | koff (s−1)a | Kd (nM)a | t1/2 (s) | |
| Compound 3 | ||||
| Con1 | (4.6 ± 0.4)E+04 | (7.6 ± 0.0)E−05 | 1.6 ± 0.1 | 9,150 |
| 1a_18 | (4.7 ± 1.6)E+04 | (5.7 ± 1.4)E−04 | 14 ± 8 | 1,211 |
| 1b J4 | (3.5 ± 0.1)E+04 | (7.1 ± 2.6)E−05 | 2.1 ± 0.8 | 9,831 |
| 1a_H77 | (3.6 ± 1.7)E+04 | (3.0 ± 8.3)E−04 | 8.6 ± 1.7 | 2,321 |
| Compound 4 | ||||
| Con1 | (3.1 ± 0.4)E+04 | (1.2 ± 0.1)E−04 | 4.0 ± 0.9 | 5,764 |
| 1a_18 | (3.5 ± 1.3)E+04 | (2.7 ± 0.5)E−03 | 80 ± 15 | 256 |
| 1b J4 | (2.8 ± 0.1)E+04 | (6.5 ± 4.6)E−05 | 2.3 ± 1.7 | 10,602 |
| 1a_H77 | (2.3 ± 0.1)E+04 | (8.8 ± 0.3)E−04 | 38 ± 0.5 | 786 |
| GSK625433 | ||||
| Con1 | (6.5 ± 1.5)E+04 | (6.6 ± 3.6)E−05 | 0.98 ± 0.3 | 10,501 |
| 1a_18b | NAd | NA | 110 ± 90 | NA |
| 1b J4 | (5.6 ± 0.9)E+04 | (5.8 ± 5.6)E−05 | 0.98 ± 0.9 | 11,925 |
| 1a_H77c | (1.1 ± 0.1)E+05 | (1.2 ± 0.0)E−02 | 110 ± 4.2 | 60 |
| HCV-796 | ||||
| Con1 | (7.2 ± 0.6)E+03 | (1.2 ± 0.3)E−04 | 16 ± 3 | 6,011 |
| 1a_18 | (1.4 ± 0.1)E+05 | (1.4 ± 0.1)E−03 | 10 ± 2 | 485 |
| 1b J4 | (2.2 ± 0.3)E+03 | (3.3 ± 0.4)E−04 | 150 ± 0.4 | 2,117 |
| 1a_H77 | (2.3 ± 0.2)E+05 | (3.4 ± 0.2)E−03 | 15 ± 1 | 204 |
a
Values are means ± standard deviations from at least two independent experiments.
b
Data were analyzed using the steady-state model (yielding only a global Kd) because the kinetics were too fast to fit properly using a kinetic model (see Materials and Methods).
c
Data were analyzed using a heterogeneous ligand binding model because the standard 1:1 binding model did not properly fit the data (see Materials and Methods).
d
NA, not applicable.