Table 1.
Niclosamide and related compounds are potent inhibitors of TMEM16A conductivity that block histamine depolarization of human airway smooth muscle cells and relax mouse tracheal rings pre-contracted with carbachol.
| Compound | TMEM16A eYFP Assay (IC50, μM) | Histamine Depolarization of ASM Cells (IC50, μM) | Bronchodilation of Mouse Tracheal Rings (EC50, μM) | TMEM16A Chloride Current (IC50, μM) | CFTR Chloride Current (IC50, μM) |
|---|---|---|---|---|---|
| Niclosamide (Cpd 1) | 0.132 ± 0.067 (42) | 0.389 ± 0.478 (3) | 0.379 ± 0.082(5)† | 2.37 ± 2.11 (7) | >30 |
| Cpd 2 | 0.196 ± 0.105 (3) | 0.044 | 0.483†, 0.585§ | 0.70 ± 0.53 (11) | >30 |
| Cpd 3 | 0.184 ± 0.089 (4) | 0.017 ± 0.000 (2) | 0.606 ± 0.003 (2)§ | 0.61 ± 0.62 (6) | nd |
| Cpd 4 | 0.901 ± 0.524 (53) | 0.178 ± 0.007 (3) | 0.467 ± 0.167 (4)† | 0.62 ± 0.37 (9) | >30 |
| Cpd 5 | 0.370 ± 0.131 (42) | 0.071 ± 0.020 (26) | 1.125† | 2.26 ± 0.65 (3) | nd |
| Nitazoxanide | 1.23 | nd | nd | 1.26 ± 1.31 (3) | nd |
| Tizoxanide | 0.398 | nd | 3.902† | 4.42 ± 2.40 (2) | nd |
| NTTP | 2.476 ± 1.236 (46) | 25.250 ± 5.445 (2) | 7.61§ | 4.69 | nd |
| 1PBC | 1.523 ± 1.360 (17) | 0.964 ± 0.756 (7) | 1.769† | 2.81 ± 1.25 (6) | >30 |
| Benzbromarone | 1.508 ± 0.504 (58) | 0.208 ± 0.248 (6) | 1.285 ± 0.211 (4)† | 4.09 ± 2.08 (6) | 5.2 |
| Dichlorophen | 4.365 ± 1.210 (58) | 0.938 ± 0.36 (29) | 2.012† | 4.66 ± 2.20 (3) | nd |
| Niflumic Acid | 26.570 ± 11.800 (55) | 6.285 ± 1.59 (4) | 51.204† | 8.54 ± 6.75 (7) | >30 |
| CaCCinh-A01 | 8.125 ± 2.720 (58) | 4.761 ± 1.23 (9) | 13.529† | 7.57 ± 3.96 (7) | 10.08 |
| MONNA | 6.295 ± 1.470 (19) | 0.201 ± 0.162 (2) | 3.023† | 13.60 ± 9.76 (4) | 18.99 |
| T16Ainh-A01 | >50.000 ± 0.0 (16) | >30 (partial) | >50.000 ± 0.0 (2)† | >30.000 ± 0.0 (7) | >30 |
Values are Mean ± SD (N) from dose-response analysis of IC50 (μM) for inhibition of responses or EC50 (μM) for bronchodilating airways (nd, not done). All CFTR IWB electrophysiology studies (eight concentration dose-response, N of 3–4 per concentration) included the benchmark inhibitor CFTRinh-172 on every assay plate, which had an average IC50 of 0.080 ± 0.014 μM (N = 5). Mouse tracheal rings pre-contracted with either an †EC95 or §EC75 level of carbachol.