Ivacaftor

Ivacaftor (VX-770) is a potent, cell-permeable small molecule potentiator of cystic fibrosis transmembrane conductance regulator (CFTR). 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. 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. It binds CFTR directly and causes CFTR channel opening by an ATP-independent mechanism. It effectively improves sweat chloride in vivo while improving lung function when at least one G551D CFTR mutation is present.