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PMID:19153558
| Citation |
Verkman, AS and Galietta, LJ (2009) Chloride channels as drug targets. Nat Rev Drug Discov 8:153-71 |
|---|---|
| Abstract |
Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human diseases, including cystic fibrosis, macular degeneration, myotonia, kidney stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have potential applications in the treatment of some of these disorders, as well as in secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension. Modulators of GABA(A) (gamma-aminobutyric acid A) receptor chloride channels are in clinical use and several small-molecule chloride-channel modulators are in preclinical development and clinical trials. Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery. |
| Links |
PubMed PMC3601949 Online version:10.1038/nrd2780 |
| Keywords |
Chloride Channels/antagonists & inhibitors; Chloride Channels/classification; Chloride Channels/drug effects; Chloride Channels/physiology; Chlorides/metabolism; Chlorides/physiology; Cystic Fibrosis/drug therapy; Cystic Fibrosis/metabolism; Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & inhibitors; Cystic Fibrosis Transmembrane Conductance Regulator/physiology; Drug Delivery Systems/methods; Humans; Ion Channel Gating/drug effects; Ion Channel Gating/physiology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0042493: response to drug |
ECO:0000314: |
P |
Figure 2Ac depicts the increase in chloride sensing of drug by increase in pH. The quick response of chloride ions to drug implies the possibility of chloride channel drug targeting for inhibition of disease progression. |
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See also
References
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