Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 92, Issue 3, Pages 287-290Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/clpt.2012.114
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Funding
- NIDDK NIH HHS [P30 DK072517] Funding Source: Medline
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Secretory diarrhea remains a major health challenge worldwide. Excessive fluid secretion in the intestine caused by enterotoxins results in activation of luminal Cl- channels on enterocytes. The cystic fibrosis transmembrane conductance regulator (CFTR) protein is the major cyclic adenosine monophosphate (cAMP)-regulated Cl- channel activated in cholera as well as in diarrheas caused by other bacterial enterotoxins. Small-molecule screens have yielded CFTR inhibitors with half-maximal inhibitory concentration (IC50) values as low as 4 nmol/l. The data from proof-of-concept studies in animal models support the development of CFTR inhibitors for antidiarrheal therapy.
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