Strategies to investigate the mechanism of action of CFTR modulators.
The malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is associated with a wide spectrum of disease. In the search for modulators of CFTR, pharmaceutical agents have been identified that (i) act indirectly by regulating the protein kinases and phosphatases, which control CFTR, and (ii) interact directly with CFTR. Some agents modulate CFTR by altering the function of the nucleotide-binding domains (NBDs) that control channel gating, whereas others inhibit CFTR by preventing Cl- flow through the channel pore. Knowledge of CFTR modulators might lead to new understanding of the CFTR Cl- channel, its physiological role and malfunction in disease.
Department of Physiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Zhiwei
Z
Cai
Toby S
TS
Scott-Ward
Hongyu
H
Li
André
A
Schmidt
David N
DN
Sheppard
D002712:Chlorides / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics
C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator