Table 2. Combination studies of SB 9200 with anti-HCV agents using HCV replicon assays.
Combination studies of SB 9200 with other anti-HCV agents were carried out using the HCV genotype 1b CON1 sub-genomic replicons. All compounds were dissolved in DMSO to get 100mM stock solution. Before initiating combination studies, the anti-HCV activity of individual compounds was determined using protocols described in the primary assays. Synergy studies were initiated by combining SB 9200 with each agent in different ratios based on individual EC50 values to achieve equipotent anti-HCV activity of each combination.
| SB 9200 | EC50 (μM) (individual agent) | Ratio | EC50 (μM) | EC90 (μM) | CC50 (μM) | S.I. (CC50/EC50) | Type of Interaction |
|---|---|---|---|---|---|---|---|
|
| |||||||
| SB 9200 | 1.0 ± 0.2 | N/A | 1.0 ± 0.2 | 6.0 | >100 | >100 | N/A |
|
| |||||||
| + IFN α | 2.1 ± 0.2 | 3:1 | 0.662 ± 0.072 | 2.8 | >100 | >151 | Synergistic |
| 1:1 | 0.643 ± 0.060 | 2.9 | >100 | >156 | Synergistic | ||
| 1:3 | 0.658 ± 0.055 | 8.8 | >100 | >152 | Synergistic | ||
|
| |||||||
| + Ribavirin | >30 | 1:30 | 2.3 ± 0.3 | >100 | >43 | Synergistic | |
|
| |||||||
| + Ribavirin (30μM) + IFN α | N/A | 3:1 | 0.777 ± 0.087 | 2.7 | >100 | >129 | Synergistic |
| 1:1 | 0.629 ± 0.082 | 2.6 | >100 | >159 | Synergistic | ||
| 1:3 | 0.686 ± 0.099 | 2.5 | >100 | >146 | Synergistic | ||
|
| |||||||
| + 2CMeCyt (NM 283) | 1.4 ± 0.1 | 3:1 | 0.522 ± 0.046 | 1.3 | >100 | >192 | Synergistic |
| 1:1 | 0.494 ± 0.050 | 1.8 | >100 | >202 | Synergistic | ||
| 1:3 | 0.462 ± 0.061 | 1.5 | >100 | >216 | Additive | ||
|
| |||||||
| + VX-950 (telaprevir) | 0.250 ± 0.024 | 100:1 | 0.108 ± 0.028 | 0.95 | >100 | >926 | Synergistic |
| 30:1 | 0.126 ± 0.026 | 1.0 | >100 | >794 | Synergistic | ||
| 10:1 | 0.118 ± 0.023 | 0.93 | >100 | >847 | Synergistic | ||
1
Synergy analysis using CalcuSynTM program (Biosoft, Inc.) (B. E Korba (1996) Antiviral Res. 29:49). N/A not applicable.