Ivacaftor-d4  (Synonyms: VX-770-d4)

Ivacaftor-d4 (VX-770-d4) is the deuterium labeled-Ivacaftor (HY-13017). Ivacaftor is a potent and orally active CFTR potentiator, targeting G551D-CFTR and F508del-CFTR with EC₅₀s of 100 nM and 25 nM, respectively^[1].

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 value of 0.236 ± 0.200 μM, a 10-fold shift in potency compared to the F508del HBEs^[3].
In recombinant cells, Ivacaftor increases CFTR channel open probability (Po) in both the F508del processing mutation and the G551D gating mutation. Ivacaftor increases forskolin-stimulated I_T in temperature-corrected F508del-FRT cells by appr 6-fold with an EC₅₀ of 25 nM^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

396.52

C₂₄H₂₄D₄N₂O₃

Solid

White to off-white

O=C(C1=CNC2=C(C1=O)C([2H])=C([2H])C([2H])=C2[2H])NC3=CC(O)=C(C(C)(C)C)C=C3C(C)(C)C

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [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  [Content Brief]

  [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  [Content Brief]

  [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):9776-9  [Content Brief]

  [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.  [Content Brief]