Table 5.
Kinetic parameters of TMC647055 interactions with different NS5B mutantsa
| Mutation | kon (1/Ms) | koff (1/s) | KD (M) | t1/2 (min) | n |
|---|---|---|---|---|---|
| Con1b wild type | 2.2E+04 | 8.9E−05 | 4.1E−09 | 130.5 | 11 |
| L392I (NNI-1) | 1.8E+04 | 9.7E−04 | 5.5E−08 | 11.9 | 2 |
| V494A (NNI-1) | 5.5E+04 | 8.4E−04 | 1.6E−08 | 13.8 | 2 |
| P495L (NNI-1) | 3.4E+03 | 2.2E−02 | 6.5E−06 | 0.5 | 2 |
a
The interaction was analyzed using the SPR reversible capture assay for HCV NS5B. For each inhibitor class, major mutations associated with reduced susceptibility to this class of inhibitors were engineered into the genotype 1b backbone. n, number of independent measurements. Values are averages of at least two independent experiments.