Table 3.
Enzyme IC50 of telaprevir and other protease inhibitors against NS3 variantsa
| Variant | Telaprevir |
Boceprevir |
Ciluprevir |
Danoprevir |
||||
|---|---|---|---|---|---|---|---|---|
| IC50(1 h) (μM) | FC | IC50(1 h) (μM) | FC | IC50 (μM) | FC | IC50 (μM) | FC | |
| WT | 0.050 | 1.0 | 0.084 | 1.0 | 0.0087 | 1.0 | 0.0073 | 1.0 |
| V36L | 0.099 | 2.0 | ND | ND | ND | ND | ND | ND |
| V36M | 0.27 | 5.4 | 0.37 | 4.4 | 0.010 | 1.2 | 0.0071 | 1.0 |
| R155I | 0.88 | 18 | ND | ND | 0.14 | 16 | ND | ND |
| R155K | 0.51 | 10 | 0.87 | 10 | 0.60, >0.84 | 69, >97 | 0.26 | 35 |
| R155S | 1.2 | 23 | ND | ND | 0.72, >0.84 | 83, >97 | ND | ND |
| R155T | 0.49 | 9.8 | ND | ND | 0.22 | 25 | ND | ND |
| A156S | 2.5 | 50 | 3.1 | 37 | 0.072 | 8.3 | 0.043 | 6.0 |
| A156T | 19 | 380 | 26 | 310 | >0.84 | >97 | 0.028 | 3.8 |
| V36M + R155K | 3.4 | 69 | 3.3 | 39 | 0.69, >0.84 | 79, >97 | 0.48 | 66 |
a
The IC50(1 h) or IC50 was the mean of the results of 2 to 5 individual experiments. FC (fold change) was determined by dividing the mean IC50(1 h) or IC50 of a given variant by that of WT. “ND” denotes that data were not determined. “>” denotes that the IC50(1 h), IC50, or FC was greater the value presented; the actual value could not be determined since no significant reduction of HCV RNA level was observed at the maximum concentration of compound used (0.84 μM for ciluprevir).