Table 1.
HCV inhibition characteristics of leading 55 hits from n4mBid cell protection small-molecule screen.
| Effect on HCV | ||||||||||
| Compound* | CC50 (μM) | EC50 (μM) | EC90 (μM) | CC50/EC50 | SDC (μM) | Replication | IVP | Entry | % Prt1 | % Prt10 |
| A5HT | >30 | ND | ND | ND | 30 | — | — | — | 12 | 74 |
| Amiodarone (12) | 14 | ND | ND | ND | 5 | — | ▿▿▿ | ▿ | 14 | 81 |
| Amitriptyline | 30 | ND | ND | ND | 10 | — | ▿▿▿ | ▿ | 19 | 75 |
| Amoxapine | 17 | ND | ND | ND | 7 | — | ▿▿▿ | — | 11 | 78 |
| Amperozide | 30 | ND | ND | ND | 5 | — | — | — | 46 | 69 |
| Apigenin | >30 | ND | ND | ND | 10 | — | — | — | 14 | 87 |
| Aprindine | 18 | ND | ND | ND | 10 | ▿ | ▿▿▿ | ▿ | 24 | 66 |
| Benztropine | 40 | ND | ND | ND | 10 | — | ▿▿ | ▿ | 51 | 93 |
| BIO | 8 | 0.70 | 1.3 | 11.4 | 5 | ▿▿▿▿ | ▿▿▿▿ | — | 72 | 0 |
| Biperiden | 30 | ND | ND | ND | 10 | — | ▿▿ | ▿ | 19 | 74 |
| Bromocriptine | >30 | 2.0 | 5.4 | >15 | 10 | ▿▿▿▿ | ▿▿▿ | ▿ | 12 | 70 |
| (±)-Butaclamol | 35 | ND | ND | ND | 10 | — | — | ▿ | 7 | 48 |
| CGS-12066A | 17 | 6.8 | 10.5 | 2.5 | 10 | ▿▿▿▿ | ▿▿▿▿ | ▿▿ | 12 | 75 |
| Cilnidipine | 20 | 4.9 | 10.0 | 4.1 | 10 | ▿▿▿▿ | ▿▿▿▿ | ▿▿ | 17 | 97 |
| Cinnarizine | >30 | ND | ND | ND | 10 | — | — | — | 16 | 68 |
| CPTA | >30 | ND | ND | ND | 10 | — | — | — | 15 | 86 |
| Cyproheptadine (12) | 17 | ND | ND | ND | 5 | — | ▿ | — | 24 | 74 |
| DKI | 18 | ND | ND | ND | 10 | — | — | — | 30 | 86 |
| Ebselen | >30 | ND | ND | ND | 30 | — | — | ▿ | 11 | 91 |
| Etazolate | >60 | 8.0 | 18.0 | >7.5 | 30 | ▿▿▿▿ | ▿▿▿▿ | ▿ | 15 | 80 |
| 5EIA | 17 | ND | ND | ND | 5 | — | ▿▿▿ | — | 8 | 58 |
| Felodipine | >30 | 9.5 | 23.0 | >3.2 | 30 | ▿▿▿▿ | ▿▿▿▿ | ▿▿ | 13 | 59 |
| Flunarizine | 18 | 2.1 | 5.2 | 8.6 | 10 | ▿ | ▿▿ | — | 73 | 85 |
| Fluphenazine (12) | 17 | 4.1 | 8.9 | 4.1 | 10 | ▿ | — | ▿▿▿▿ | 65 | 0 |
| Forskolin | >30 | ND | ND | ND | 10 | — | + | — | 17 | 71 |
| GR 127935 | 7 | 1.6 | 4.0 | 4.4 | 3 | ▿ | ▿ | ▿▿▿▿ | 84 | 0 |
| GR 89696 | 45 | ND | ND | ND | 10 | — | ▿ | ▿ | 11 | 58 |
| GW2974 | 25 | 3.1 | 9.0 | 8.1 | 10 | ▿▿▿▿ | ▿▿▿▿ | ▿▿ | 17 | 68 |
| Ifenprodil | 16 | ND | ND | ND | 10 | ▿ | — | ▿ | 14 | 58 |
| IPFME | 17 | ND | ND | ND | 10 | — | ▿▿▿ | ▿ | 12 | 59 |
| MK-886 (12, 21) | >30 | 7.5 | 11.0 | >4.0 | 10 | — | ▿ | ▿ | 12 | 96 |
| Nemadipine-A | >30 | 10.5 | 31.0 | >2.9 | 30 | ▿▿▿▿ | ▿▿▿▿ | ▿ | 16 | 69 |
| PCperazine (12) | 16 | 4.2 | 9.5 | 3.8 | 10 | ▿ | ▿ | ▿▿▿▿ | 20 | 62 |
| PD 404,182 | >60 | 12.0 | 41.0 | >5.0 | 30 | — | ▿▿ | ▿▿▿▿ | 18 | 70 |
| Perphenazine | 22 | ND | ND | ND | 10 | — | — | ▿▿ | 18 | 81 |
| Pimozide | 7 | ND | ND | ND | 5 | — | ▿ | ▿ | 49 | 79 |
| PPM | 16 | ND | ND | ND | 10 | — | ▿▿ | ▿▿ | 16 | 68 |
| Protriptyline | 16 | ND | ND | ND | 10 | — | ▿ | ▿ | 32 | 74 |
| Psora-4 | >30 | 5.7 | 10.0 | >5.3 | 10 | ▿▿▿ | ▿▿▿ | — | 14 | 66 |
| 6PTN | >60 | ND | ND | ND | 30 | ▿▿ | ▿▿ | — | 16 | 70 |
| Quinidine | 23 | 4.2 | 9.0 | 5.5 | 15 | ▿ | ▿▿▿▿ | ▿ | 44 | 60 |
| Quipazine-6N | 28 | ND | ND | ND | 10 | — | — | ▿▿ | 13 | 74 |
| Raloxifene | 7 | ND | ND | ND | 5 | ▿▿ | ++ | ▿▿ | 79 | 0 |
| Ritanserin | 17 | ND | ND | ND | 10 | — | — | ▿ | 57 | 72 |
| Ro 25–6981 | >30 | ND | ND | ND | 30 | — | — | ▿ | 18 | 65 |
| SB 222200 | >30 | 6.6 | 30.0 | >4.5 | 30 | ▿▿▿▿ | ▿▿▿▿ | ▿▿▿ | 16 | 73 |
| SB 224289 | 15 | ND | ND | ND | 5 | ▿ | ▿▿ | ▿▿ | 20 | 66 |
| SKF-38393AH | >30 | ND | ND | ND | 30 | ▿ | ▿▿ | — | 13 | 56 |
| SKF-95282 | 17 | ND | ND | ND | 10 | ▿ | ▿▿ | ▿ | 16 | 63 |
| TFP | 16 | ND | ND | ND | 8 | ▿ | ▿▿▿ | ▿ | 19 | 57 |
| (R,R)-THC | 14 | 4.5 | 9.7 | 3.1 | 10 | ▿▿▿▿ | ▿▿▿▿ | ▿▿ | 16 | 62 |
| TMB | 14 | ND | ND | ND | 10 | — | — | ▿ | 15 | 78 |
| Trifluoperazine (12) | 18 | 6.5 | 11.0 | 2.8 | 10 | ▿ | ▿▿ | ▿▿▿ | 15 | 78 |
| TTNPB (22) | 42 | 9.1 | 22.0 | 4.6 | 30 | ▿▿▿▿ | ▿▿▿▿ | — | 35 | 102 |
| U-74389G | >30 | ND | ND | ND | 5 | — | ++ | ▿ | 59 | 47 |
| 2′CMA | 18 | 0.09 | 0.24 | 200 | 1 | ▿▿▿▿ | ▿▿▿▿ | — | 94 | 71 |
| VX-950 | 30 | 0.20 | 0.60 | 150 | 1 | ▿▿▿▿ | ▿▿▿▿ | — | ND | ND |
| Mock | NA | NA | NA | NA | NA | — | — | — | 8 | 8 |
CC50 and EC50 values are from n4mBid dose–response profiles in the absence and presence of HCV infection, respectively (Fig. S2). SDC, selected drug concentration for HCV life cycle studies; IVP, infectious virus production; % Prt1 and % Prt10, n4mBid cell death protection in screen as a percentage of mock-infected cells at 1 and 10 μM, respectively (mock, 0.1% DMSO); ND, not determined; NA, not applicable; boldface entries are controls. ▿, 40–60% inhibition; ▿▿, 61–80% inhibition; ▿▿▿, 81–90% inhibition; ▿▿▿▿, >90% inhibition. +, 1.5- to 2-fold enhancement; ++, >2-fold enhancement; —, <40% inhibition or <50% enhancement. Replication and IVP levels are based on Fig. S4. Entry levels are based on Fig. S3. All inhibition and enhancement levels are relative to cells mock-treated with 0.1% DMSO in growth media.
*Complete names of compounds can be found in Table S1. References to compounds with known anti-HCV activity are indicated in parentheses.