期刊
NATURE REVIEWS DRUG DISCOVERY
卷 8, 期 2, 页码 153-171出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nrd2780
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资金
- NEI NIH HHS [R01 EY013574] Funding Source: Medline
- NHLBI NIH HHS [R01 HL073856, R01 HL059198] Funding Source: Medline
- NIBIB NIH HHS [R37 EB000415] Funding Source: Medline
- NIDDK NIH HHS [R37 DK035124, P30 DK072517] Funding Source: Medline
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.
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