The cystic fibrosis (CF) gene encodes a cAMP-regulated chloride channel, the CF transmembrane conductance regulator (CFTR).{25612} A glycine-to-aspartic acid missense mutation at codon 551 (G551D) is a common mutation associated with a severe CF phenotype.{25612} Ivacaftor is an orally bioavailable CFTR potentiator that improves chloride transport. It increases the forskolin-induced CFTR-mediated epithelial current in cells expressing the G551D mutation by ~4-fold (EC50 = 100 nM) but has no effect on current in the absence of forskolin.{25614} Ivacaftor increases chloride secretion in cultured human CF bronchial epithelial cells carrying the G551D mutation on one allele and the common F508del processing mutation on the other allele.{25614} It binds CFTR directly and causes CFTR channel opening by an ATP-independent mechanism.{25613} It effectively improves sweat chloride in vivo while improving lung function when at least one G551D CFTR mutation is present.{25611}
产品描述
An orally bioavailable CFTR potentiator that improves chloride transport; increases the forskolin-induced CFTR-mediated epithelial current in cells expressing the G551D mutation by ~4-fold (EC50 = 100 nM); increases chloride secretion in cultured human CF bronchial epithelial cells carrying the G551D mutation
