TABLE 2.
Replication fitness and resistance phenotype of AG-021541-resistant replicon cell linesa
| Selection method and AG-21541 concn | No. of cell lines | Range (median) of fold change in EC50
|
Median RLuc activity | |
|---|---|---|---|---|
| AG-021541 | IFN | |||
| Serial passage | ||||
| 1.6× EC90 | 9 | 6-58 (33) | 0.8-2.4 (1.5) | 133,000 |
| 3.2× EC90 | 8 | 9-150 (62) | 0.6-1.4 (0.9) | 51,000 |
| 6.4× EC90 | 7 | 37-104 (100) | 0.4-3.6 (1.1) | 12,000 |
| Direct colony formation | ||||
| 3× EC90 | 6 | 28-47 (36) | 0.4-1.9 (1.4) | 526,000 |
| 6× EC90 | 5 | 27-246 (128) | 1.3-2.0 (1.5) | 16,000 |
a
Stable cell lines obtained at various concentrations of AG-021541 either by serial passages or direct colony formation were evaluated for their replication fitness and susceptibility to AG-021541 and IFN in the reporter replicon assay. Cells were exposed to compounds for 3 days before RLuc activity was determined.