Ivacaftor is an orally bioavailable CFTR potentiator, used for cystic fibrosis treatment.

Ivacaftor (10 µM) increases the PC secretion activity by 3-fold for ABCB4-G535D, 13.7-fold for ABCB4-G536R, 6.7-fold for ABCB4-S1076C, 9.4-fold for ABCB4-S1176L, and 5.7-fold for ABCB4-G1178S. Ivacaftor corrects the functional defect of ABCB4 mutants^[1]. Ivacaftor (10 μM) significantly increases CFTR activity in W1282X-expressing cells compared to R1162X CFTR cells^[2]. Ivacaftor shows no significant activity against 160 targets tested including the GABA_A benzodiazepine receptor. Ivacaftor increases the chloride secretion with an EC₅₀ of 0.236 ± 0.200 μM, a 10-fold shift in potency compared to the F508del HBEs^[3]. In recombinant cells, VX-770 increases CFTR channel open probability (Po) in both the F508del processing mutation and the G551D gating mutation. VX-770 increases forskolin-stimulated I_T in temperature-corrected F508del-FRT cells by appr 6-fold with an EC₅₀ of 25 nM^[4].

Ivacaftor (1-200 mg/kg, p.o.) exhibits good oral bioavailability in rat^[3].

• [1]. Delaunay JL, et al. Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770). Hepatology. 2017 Feb;65(2):560-570.

  [2]. Mutyam V, et al. Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation. J Cyst Fibros. 2017 Jan;16(1):24-29.

  [3]. Hadida S, et al. Discovery of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, ivacaftor), a potent and orally bioavailable CFTR potentiator. J Med Chem. 2014 Dec 11;57(23):9776-95

  [4]. Van Goor F, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18825-30.

• [1]. Delaunay JL, et al. Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770). Hepatology. 2017 Feb;65(2):560-570.

  [2]. Mutyam V, et al. Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation. J Cyst Fibros. 2017 Jan;16(1):24-29.

  [3]. Hadida S, et al. Discovery of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, ivacaftor), a potent and orally bioavailable CFTR potentiator. J Med Chem. 2014 Dec 11;57(23):9776-95

  [4]. Van Goor F, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18825-30.

392.49

C₂₄H₂₈N₂O₃

873054-44-5

Room temperature in continental US; may vary elsewhere

10 mM in DMSO

* "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">