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CFTR Inhibitors for Treating Diarrheal Disease
Author(s) -
Thiagarajah J R,
Verkman A S
Publication year - 2012
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2012.114
Subject(s) - cystic fibrosis transmembrane conductance regulator , secretion , cystic fibrosis , cyclic adenosine monophosphate , enterotoxin , cholera toxin , diarrhea , adenosine , cholera , chemistry , ic50 , chloride channel , pharmacology , biology , microbiology and biotechnology , biochemistry , medicine , escherichia coli , in vitro , gene , receptor
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 (IC 50 ) 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. Clinical Pharmacology & Therapeutics (2012); 92 3, 287–290. doi: 10.1038/clpt.2012.114
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