Table 1.
Pharmacology of CaCC ANO1/TMEM16A inhibitors.
| Inhibitor | Structure | IC50 (μmol/L) | Test assay | Selectivity | Effect | Ref. |
|---|---|---|---|---|---|---|
| NFA |  |
7–37 | Xenopus oocytes | KCa channel (+) | Anti-cancer, | 38, 39, 40, 41, 42 |
| mANO1-CHO | Kv4 channel (−) | Anti-asthma | ||||
| VRAC (−) | ||||||
| ANO6 (−) | ||||||
| [Ca2+]i (+) | ||||||
| FFA |  |
14–35 | Xenopus oocytes | KCa channel (+) | NR | 38,39 |
| mANO1-CHO | [Ca2+]i (+) | |||||
| NPPB |  |
22–68 | Xenopus oocytes | K+ channel (−) | Anti-cancer, | 38,39,43,44 |
| mANO1-CHO | [Ca2+]i (+) | Antinociception | ||||
| VRAC (−) | ||||||
| DIDS |  |
11–550 | Xenopus oocytes | Kv4 channel (−) | Anti-cancer, | 38,39,44, 45, 46, 47 |
| mANO1-CHO | VRAC (−) | Antinociception | ||||
| [Ca2+]i (+) | ||||||
| TRPV1 (+) | ||||||
| xBest2a (/) | ||||||
| Dichlorophen |  |
5.5 | ANO1-HEK293 | ANO2 (−) | Anti-asthma | 48 |
| CFTR (/) | ||||||
| ENaC (/) | ||||||
| Benzbromarone |  |
10 | ANO1-HEK293 | ANO2 (−) | Anti-asthma | 48 |
| CFTR (/) | ||||||
| ENaC (/) | ||||||
| CaCCinh-A01 |  |
1–7.8 | HT-29 | hBest1 (–, 7 μmol/L) | Anti-cancer, | 38,47,49, 50, 51, 52, 53, 54, 55, 56 |
| hNO1-FRT | ANO2 (−) | Anti-hypertension, | ||||
| mANO1-CHO | CFTR (/) | Anti-diarrhea, | ||||
| VRAC (−) | Antinociception, | |||||
| [Ca2+]i (/) | Anti-high glucose induced renal cyst growth, | |||||
| xBest2a (/) | Anti-ischemic stroke induced BBB intergrity | |||||
| T16Ainh-A01 |  |
1 | hANO1-HEK293 | ANO2 (−) | Anti-cancer, | 38,47,50,52,54,57, 58, 59, 60 |
| CFTR (/) | Anti-hypertension, | |||||
| [Ca2+]i (/) | Anti-Asthma, | |||||
| hBest1 (/) | Antinociception, | |||||
| VGCC (–, 50 nmol/L) | Anti-eosinophilic esophagitis, | |||||
| xBest2a (/) | ||||||
| MONNA |  |
1.27 | hANO1-HEK293 | VRAC (−) | Anti-cancer, | 47,61, 62, 63, 64, 65 |
| xANO1 (0.08 μmol/L) | ANO2 (−) | Anti-itch, | ||||
| mBest1 (/) | Anti-hypertension, | |||||
| hBest1 (/) | Anti-polyfertilization | |||||
| mCLC2 (/) | ||||||
| hCFTR (/) | ||||||
| xBest2a (/) | ||||||
| Ani9 |  |
0.08 | hANO1-FRT | ANO2 (/) | Anti-cancer, | 47,57,65,66 |
| CFTR (/) | Anti-polyfertilization | |||||
| ENaC (/) | ||||||
| VRAC (/) | ||||||
| ANO6 (slower activation) | ||||||
| xBest2a (/) | ||||||
| 10bm |  |
0.03 | hANO1-FRT | ANO2 (–, 0.4 μmol/L) | NR | 67 |
| CFTR (/) | ||||||
| Ani9-5f |  |
0.02 | hANO1-FRT | ANO2 (/) CFTR (/) | Anti-cancer | 68 |
| Dimer trans-ε-viniferin (TV) |  |
1.1 | HT-29 | CFTR (−) | Anti-diarrhea | 69 |
| Tetramer, γ-2-viniferin (RV) |  |
12.3 | HT-29 | CFTR (−) | Anti-diarrhea | 69 |
| Niclosamide |  |
0.1–2.4 | hANO1-HEK293T | CFTR (/) | Anti-asthma | 42,66,70 |
| ANO6 (−) | ||||||
| [Ca2+]i (−) | ||||||
| Tannic acid |  |
6–25 | hANO1-FRT | CFTR (/) | Anti-nociception, | 38,50,62,71, 72, 73 |
| mANO1-CHO | ENaC (/) | Anti-cancer, | ||||
| hBest1 (–, 15 μmol/L) | Anti-asthma | |||||
| ANO2 (−) | ||||||
| Eugenol |  |
150 | hANO1-FRT T84 cell |
CFTR (/) | Anti-diarrhea, | 74, 75, 76 |
| [Ca2+]i (/) | Local analgesia | |||||
| Nav1.8 (−) | ||||||
| TRPV1 (−) | ||||||
| Kv1.5 (−) | ||||||
| VGCC (−) | ||||||
| Galangin |  |
4.5–9.7 | mANO1-CHO | NR | Anti-cancer | 77,78 |
| Luteolin |  |
9.37 | hANO1-FRT | ANO2 (–, 120 μmol/L) | Anti-cancer | 77, 78, 79 |
| mANO1-CHO | L-type Ca2+ channel (−) | |||||
| [Ca2+]i (/) | ||||||
| Quercetin |  |
13.7 | mANO1-CHO | NKCC1 (+) | Anti-cancer, | 78,80 |
| Na+-K+-ATPase (+) | Attenuation of GI tract motility, | |||||
| CFTR (+) | Increasement of intestinal Cl– secretion | |||||
| K+ channel (+) | ||||||
| TRPM7 (−) | ||||||
| Idebenone |  |
9.2 | hANO1-FRT | ANO2 (−) | Anti-cancer, | 81,82 |
| CFTR (/) | Anti-renal cyst | |||||
| [Ca2+]i (/) | ||||||
| Plumbagin |  |
12.46 | hANO1-FRT | CFTR (−) | Anti-cancer, | 81,83 |
| K+ channel (/) | Anti-diarrhea | |||||
| Na+-K+-ATPase (/) | ||||||
| [Ca2+]i (/) | ||||||
| Avermectins |  |
0.15–1.32 | mANO1-CHO | NR | Anti-cancer | 84 |
+, activation effect; –, inhibitory effect; /, no effect; NR, no report; NKCC, Na+/K+/Cl– co-transporter.