Ivacaftor

Product Description

Ivacaftor is a potent and selective potentiator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that targets F508del-CFTR and G551D-CFTR (EC₅₀ values are 25 nM and 100 nM, respectively); its potentiation activity depends on the level of CFTR phosphorylation. Ivacaftor reversibly binds to wild type (WT-CFTR) and G551D-CFTR mutants, increasing the open probability via an ATP-independent mechanism, and enhances cAMP/PKA-signaling mediated gating activity for both WT-CFTR and G551D-CFTR mutants. In cultured human CF bronchial epithelia with G551D/F508del mutations, Ivacaftor increases Forskolin (Cat. No. 1099)-induced transepithelial current (EC₅₀ = 236 nM) and increases chloride secretion by 10-fold. Also rescues endothelial CFTR expression and function and prevents endothelial barrier failure and protein leak in human pulmonary microvascular endothelial cells. Ivacaftor is orally bioavailable.

Solubility

Preparing Stock Solutions for Ivacaftor

The following data is based on the product molecular weight 392.50

Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which all affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:

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Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.55 mL	12.74 mL	25.48 mL
5 mM	0.51 mL	2.55 mL	5.10 mL
10 mM	0.25 mL	1.27 mL	2.55 mL
50 mM	0.05 mL	0.25 mL	0.51 mL

Calculators

Background References

References are publications that support the biological activity of the product.

• Nguyen Modulation of cAMP metabolism for CFTR potentiation in human airway epithelial cells. Sci.Rep. 2021 PMID: 33441643
• Eckford 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 manner. J.Biol.Chem. 2012 PMID: 22942289
• Levring CFTR function, pathology and pharmacology at single-molecule resolution. Nature 2023 PMID: 36949202
• Erfinanda Loss of endothelial CFTR drives barrier failure and edema formation in lung infection and can be targeted by CFTR potentiation. Sci.Transl.Med. 2022 PMID: 36475904
• Cui VX-770-mediated potentiation of numerous human CFTR disease mutants is influenced by phosphorylation level. Sci.Rep. 2019 PMID: 31530897
• Jih Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle. Proc.Natl.Acad.Sci.U.S.A. 2013 PMID: 23440202