Table 3.
Potencies and efficacies of hERG blockers identified from primary qHTS (thallium influx), confirmation (thallium influx), and patch clamp assays
| Compound | qHTS (two runs) | Confirmation | Patch clamp | ||
|---|---|---|---|---|---|
| IC50 | Efficacy | IC50 | Efficacy | IC50 | |
| 1,3-diphenylguanidine | 3.4 ± 0.3 | 56 ± 7 | 6.9 ± 3 | 39 ± 12 | 13 |
| 2-aminoanthracene* | 6.5 ± 2.1 | 61 ± 3 | 17.5 ± 26 | 67 ± 19 | >100 |
| 3,3,5-trimethylcyclohexylsalicylate | 23 ± 23 | 52 ± 6 | Inactive | ND | |
| 4-N-hexyl-4′-cyanobiphenyl | 8.2 ± 2.6 | 39 ± 6 | Inactive | ND | |
| benzethonium chloride | 2.8 ± 0.5 | 91 ± 1 | 3.6 ± 1.4 | 77 ± 9 | 0.98 |
| curcumin* | 2.6 ± 0.9 | 129 ± 4 | 4.4 ± 1.4 | 140 ± 4 | 22 |
| D&C red dye 27* | 4.5 ± 0.7 | 119 ± 5 | 7.0 ± 2.5 | 173 ± 41 | >100 |
| domiphen bromide | 7.0 ± 2.8 | 78 ± 0.6 | 4.3 ±1.0 | 62 ± 11 | 1.5 |
| econazole nitrate | 9.1 ± 2.9 | 109 ± 8 | 7.2 ± 2.8 | 112 ± 11 | 3.5 |
| malachite green oxalate | 7.1 ± 0 | 97 ± 3 | 4.8 ± 0.8 | 108 ± 7 | 1.9 |
| o,p′-DDT | 17 ± 11 | 56 ± 2 | 22.2 ± 4.1 | 58 ± 8 | 2.6 |
| quinidine | 11 ± 5.6 | 107 ± 25 | 13.6 ± 5.4 | 110 ± 13 | 2.1 |
| reserpine | 7.5 ± 3.5 | 125 ± 23 | 4.9 ± 1.7 | 118 ± 7 | 1.9 |
| tamoxifen, citrate salt | 6.4 ± 1.0 | 106 ± 22 | 8.3 ± 0.8 | 110 ± 4 | 4.2 |
| tetra-n-octylammonium bromide | 0.38 ± 0.03 | 102 ± 4 | 0.26 ± 0.1 | 100 ± 3 | 0.082 |
| tricresyl phosphate | 14 ± 9 | 82 ± 11 | 9.7 ± 1.6 | 68 ± 16 | 8.8 |
| trixylenyl phosphate | 39 ± 45 | 67 ± 12 | 15.9 ± 11 | 43 ± 15 | >100 |
| verapamil | 3.1 ± 1.2 | 105 ± 1 | 3.4 ± 0.8 | 100 ± 8 | 0.2 |
| zinc pyrithione* | 3.5 ± 1.4 | 155 ± 9 | 3.4 ± 0.3 | 178 ± 7 | 33 |
Abbreviations: DDT = 1,1,1-trichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane; ND = not determined
*
Inhibition was found in wild type cells.
Each value of potency (IC50, μM) and efficacy (inhibition of thallium influx as a % of positive control) is the mean ± SD of the results from two runs of primary screening and from three experiments, with each concentration tested in duplicate, in the confirmation assay.