title: CFTR inhibitors for treating diarrheal disease.
abstract: 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.
authors: Department of Medicine, University of California-San Francisco, CA, USA.
authors: J R
authors: JR
authors: Thiagarajah
authors: A S
authors: AS
authors: Verkman
mesh_terms: D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors* / Q000502:physiology; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004768:Enterotoxins / Q000009:adverse effects; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000930:Antidiarrheals; C505032:CFTR protein, human; D018118:Chloride Channels; D004768:Enterotoxins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator