TABLE 1.
Summary of hits from primary screen and secondary validation assays
| Primary hit | Primary screen |
Secondary validation screen |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Gluc assay |
ATPlite assay |
HCV-Luc assayc | ATPlite assayc | 2-Part HCV infection core-staining assay |
|||||
| Curve class | EC50 (μM) | Efficacy (%) | Curve class | CC50 (μM) | Part 1 (EC50 [μM]) | Part 2 (EC50 [μM]) | |||
| Amperozide hydrochloride | 2 | 7.31 | 92.2 | 4 | >42.0 | 11.9 ± 5.38 | 92.3 ± 3.09 | 1.70 | 2.49 |
| Anthraquinoneb | 1 | 3.66 | 83.0 | 3 | 25.9 | 0.310 ± 0.0900 | 74.5 ± 13.8 | >30.0 | >30.0 |
| Benztropine mesylate | 2 | 3.66 | 55.7 | 4 | >42.0 | 12.6 ± 2.63 | 82.0 ± 6.16 | 2.55 | 2.65 |
| BIO | 1 | 2.06 | 70.1 | 4 | >42.0 | 1.29 ± 0.610 | 88.1 ± 15.5 | >30.0 | 6.48 |
| cis-(Z)-flupenthixol dihydrochloride | 2 | 2.06 | 73.9 | 3 | 20.6 | 4.77 ± 1.49 | 97.8 ± 10.9 | 1.23 | 0.319 |
| Cyclosporine | 1 | 1.16 | 85.6 | 4 | >42.0 | 0.512 ± 0.0600 | 95.6 ± 13.6 | 0.321 | 0.301 |
| Diacylglycerol kinase inhibitor I | 2 | 5.80 | 84.7 | 4 | >42.0 | 35.4 ± 16.3 | 102 ± 8.87 | 12.6 | 0.541 |
| Dilazep hydrochloride | 2 | 8.20 | 116 | 4 | >42.0 | 5.49 ± 2.97 | 80.3 ± 9.86 | 4.56 | 4.38 |
| Ellipticinea | 1 | 3.26 | 90.3 | 4 | >42.0 | 0.440 ± 0.140 | 0.250 ± 0.0600 | NAd | NA |
| Emetine dihydrochloride hydratea | 1 | 0.210 | 85.6 | 3 | 25.9 | 0.360 ± 0.0150 | 35.6 ± 2.12 | NA | NA |
| Fiduxosin hydrochloride | 2 | 9.20 | 103 | 3 | 25.9 | 1.18 ± 0.850 | 100 ± 2.70 | 2.87 | 1.15 |
| Flunarizine dihydrochloride | 1 | 1.64 | 73.5 | 3 | 41.1 | 27.6 ± 9.41 | 82.0 ± 8.59 | 0.613 | 0.270 |
| GR 127935 hydrochloride hydrate | 1 | 2.59 | 86.7 | 3 | 16.4 | 0.780 ± 0.690 | 78.8 ± 10.8 | 0.444 | 0.463 |
| GW2974 | 2 | 9.20 | 94.8 | 4 | >42.0 | 7.68 ± 3.76 | 91.3 ± 6.99 | 17.0 | 19.5 |
| Perphenazine | 2 | 7.31 | 113 | 3 | 16.4 | 0.810 ± 0.400 | 73.6 ± 6.65 | 4.56 | 4.31 |
| Quinacrine dihydrochloride | 2 | 5.80 | 94.9 | 3 | 20.6 | 0.510 ± 0.230 | 78.5 ± 1.20 | 2.93 | 2.81 |
| Ritanserin | 1 | 1.84 | 93.3 | 4 | >42.0 | 1.46 ± 1.09 | 91.5 ± 14.1 | 4.84 | 2.95 |
| Roscovitine | 2 | 8.20 | 90.5 | 4 | >42.0 | 27.5 ± 11.8 | 97.2 ± 10.3 | 24.6 | 19.0 |
| SB 242084 dihydrochloride hydrate | 2 | 9.20 | 93.5 | 3 | 32.6 | 32.0 ± 23.2 | 84.8 ± 15.0 | 10.8 | 4.25 |
| Thioridazine hydrochloride | 2 | 6.51 | 83.2 | 3 | 20.6 | 29.1 ± 8.39 | 98.4 ± 9.97 | 2.16 | 1.96 |
| Trifluoperazine dihydrochlorideb | 2 | 4.11 | 85.2 | 3 | 16.4 | 2.91 ± 2.02 | 99.2 ± 3.62 | 29.7 | 19.1 |
| U-73343a | 1 | 1.46 | 74.8 | 3 | >42.0 | 0.940 ± 1.22 | 0.860 ± 0.960 | NA | NA |
a
Significant cytotoxicity in the ATPlite assay of the validation screen at a concentration of 10 μM.
b
Discrepant results between the Luc-based assay and HCV core-staining assay.
c
Compounds were tested at 10-μM concentration. The numbers (means ± SD) are percentages of the DMSO control from 5 replicates.
d
NA, not applicable.