TABLE 4.
Susceptibility of the M423T mutant replicon and polymerase to PF-00868554a
| Compound | Replicon EC50 (μM)c
|
FC in EC50 | Biochemical IC50 (μM)
|
FC in IC50 | ||
|---|---|---|---|---|---|---|
| wt | M423T | NS5BΔ21 wt | NS5BΔ21M423T | |||
| PF-00868554 | 0.035 ± 0.031 | 27 ± 9 | 761 | 0.015 ± 0.010 | 11 ± 3 | 733 |
| Benzimidazole compound C | 1.6 ± 0.9 | 2.4 ± 0.7 | 1.4 | 0.20 ± 0.01b | 0.38 ± 0.03 | 1.9 |
| IFN-α | 0.97 ± 0.09 | 1.3 ± 0.2 | 1.4 | ND | ND | ND |
a
The susceptibility of the 1b Con1 wt and M423T replicon cell line to inhibitors was evaluated in the reporter replicon assay. Cells were exposed to compounds for 3 days before RLuc activity was determined. The susceptibility of the 1b Con1 wt and M423T mutant polymerase to inhibitors was evaluated in the HCV polymerase biochemical assay as described in Materials and Methods. Results represent the means ± standard deviations (three experiments) or individual values (one to two experiments of duplicates). FC, fold change; ND, not determined.
b
The result was generated against the 1b BK polymerase.
c
The replicon EC50s for IFN-α are given as IU/ml.