Ivacaftor-d₁₉is intended for use as an internal standard for the quantification of ivacaftor by GC- or LC-MS. Ivacaftor is an orally bioavailable potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) that improves chloride transport.¹It increases the forskolin-induced CFTR-mediated epithelial current in cells expressing the G551D missense mutation associated with severe cystic fibrosis by approximately 4-fold (EC₅₀= 100 nM) but has no effect on current in the absence of forskolin.¹Ivacaftor increases chloride secretion in cultured human cystic fibrosis bronchial epithelial cells carrying the G551D mutation on one allele and the common δF508 processing mutation on the other allele.¹It binds CFTR directly and leads to CFTR channel openingviaan ATP-independent mechanism.²Formulations containing ivacaftor have been used in the treatment of cystic fibrosis in patients carrying one or more mutations in theCFTRgene.

1.Van Goor, F., Hadida, S., Grootenhuis, P.D., et al.Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770Proc. Natl. Acad. Sci. U.S.A.106(44)18825-18830(2009) 2.Eckford, P.D., Li, C., Ramjeesingh, M., et al.Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent mannerJ. Biol. Chem.287(44)36639-36649(2012)