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Validation & Quality Control

Product Citations(1)

Am J Respir Crit Care Med, 2012, 186(7), 694-696

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Ivacaftor (VX-770) is available in the following compound libraries:

Chemical Library (96-well) Inhibitor Library (96-well)

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Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S6003	PTC124 (Ataluren)	<1 mg/mL	57 mg/mL	<1 mg/mL
S1565	VX-809	<1 mg/mL	91 mg/mL	16 mg/mL
S1144	Ivacaftor (VX-770)	<1 mg/mL	79 mg/mL	<1 mg/mL
S7059	VX-661	<1 mg/mL	104 mg/mL	<1 mg/mL

Product Description

Biological Activity Protocol Chemical Information Product Citations Tech Support & FAQs

Biological Activity

Description	Ivacaftor (VX-770, Kalydeco) is a potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM, respectively.
Targets	G551D-CFTR	F508del-CFTR
IC50	100 nM	25 nM ^[1]
In vitro	Ivacaftor (10 μM) significantly increases the forskolin-stimulated Cl^- secretion (I_T) by ~4-fold with an EC50 of 100 nM in the recombinant Fisher rat thyroid (FRT) cells expressing G551D gating mutation of CFTR, and by ~6-fold with an EC50 of 25 nM in the recombinant cells expressing temperature-corrected F508del processing mutation of CFTR. Consistent with the increases in the forskolin-stimulated I_T, Ivacaftor (10 μM) increases the open probability (P_o) of G551D-, F508del-, and wild-type CFTR by ~6-fold, ~5-fold and ~2-fold, respectively, indicating that Ivacaftor acts directly on CFTR to increase its gating activity. In primary cultured human CF bronchial epithelia (HBE) carrying the G551D and F508del CFTR mutations, Ivacaftor (10 μM) potently increases the forskolin-stimulated I_T by ~10-fold from 5% to a maximum level of 48% of that measured in non-CF HBE, with an EC50 of 236 nM displaying ~70-fold more potency compared with the commonly used CFTR potentiator genistein, which has an EC50 of 16 μM. In HBE with F508del homozygous CFTR, Ivacaftor causes a significant increase in the forskolin-stimulated I_T with an EC50 of 22 nM, to a less extent from 4% to 16% of non-CF HBE compared with the effect in G551D/F508del HBE. Due to CFTR potentiation, Ivacaftor inhibits excessive ENaC-mediated Na⁺ and fluid absorption with an IC50 of 43 nM, and decreases the amiloride response, resulting in an increase in the surface fluid and cilia beat frequency (CBF) in G551D/F508del HBE. ^[1]
In vivo
Clinical Trials	A Phase III study of Ivacaftor in cystic fibrosis subjects age 6 to 11 with the G551D mutation has been completed.
Features	Ivacaftor is the first potent and orally available CFTR potentiator to enter human clinical trials.

Protocol(Only for Reference)

Kinase Assay: ^[1]

Ussing Chamber Recordings	The effect of Ivacaftor on CFTR-mediated Cl^- secretion is characterized by measuring the CFTR-mediated I_T in chambers using recombinant Fisher rat thyroid (FRT) cells expressing G551D, or F508del CFTR. Cells are grown on Costar Snapwell cell culture inserts maintained at 37 °C before recording. The cell culture inserts are mounted into an Ussing chamber to record I_T in the voltage-clamp mode (V_hold = 0 mV). For FRT cells, the basolateral membrane is permeabilized with 360 μg/mL Nystatin and a basolateral to apical Cl^- gradient is established. The basolateral bath solution contains 135 mM NaCl, 1.2 mM CaCl₂, 1.2 mM MgCl₂, 2.4 mM K₂HPO₄, 0.6 mM KHPO₄, 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes), and 10 mM dextrose (titrated to pH 7.4 with NaOH). The apical NaCl is replaced by equimolar Na⁺ gluconate (titrated to pH 7.4 with NaOH). The addition of a maximally effective concentration of forskolin (10 μM) is used to stimulate I_T in the presence of various concentrations of Ivacaftor. All recordings are digitally acquired using Acquire and Analyze software. EC50 values are determined from the concentration-response curve of the increase in forskolin-stimulated I_T after application of Ivacaftor.

Ussing Chamber Recordings

The effect of Ivacaftor on CFTR-mediated Cl^- secretion is characterized by measuring the CFTR-mediated I_T in chambers using recombinant Fisher rat thyroid (FRT) cells expressing G551D, or F508del CFTR. Cells are grown on Costar Snapwell cell culture inserts maintained at 37 °C before recording. The cell culture inserts are mounted into an Ussing chamber to record I_T in the voltage-clamp mode (V_hold = 0 mV). For FRT cells, the basolateral membrane is permeabilized with 360 μg/mL Nystatin and a basolateral to apical Cl^- gradient is established. The basolateral bath solution contains 135 mM NaCl, 1.2 mM CaCl₂, 1.2 mM MgCl₂, 2.4 mM K₂HPO₄, 0.6 mM KHPO₄, 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes), and 10 mM dextrose (titrated to pH 7.4 with NaOH). The apical NaCl is replaced by equimolar Na⁺ gluconate (titrated to pH 7.4 with NaOH). The addition of a maximally effective concentration of forskolin (10 μM) is used to stimulate I_T in the presence of various concentrations of Ivacaftor. All recordings are digitally acquired using Acquire and Analyze software. EC50 values are determined from the concentration-response curve of the increase in forskolin-stimulated I_T after application of Ivacaftor.

1

References

Chemical Information

Download Ivacaftor (VX-770) SDF

Molecular Weight (MW)	392.49
Formula	C₂₄H₂₈N₂O₃
CAS No.	873054-44-5
Synonyms	N/A

Solubility (25°C) DMSO 79 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

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Research Area

Product Citations (1)

A young Hispanic with c.1646G>A mutation exhibits severe cystic fibrosis lung disease: is ivacaftor an option for therapy? [Yarlagadda S, et al. Am J Respir Crit Care Med 2012;186(7), 694-696]
PubMed: 23027855

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Ivacaftor (VX-770)

Validation & Quality Control

Product Citations(1)

Quality Control & MSDS

Related Compound Libraries

Ivacaftor (VX-770) is available in the following compound libraries:

Product Information

Compare CFTR Chemicals

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Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[1]

References

Chemical Information

Research Area

Product Citations (1)

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Cat.No.	Product Name	Water	DMSO	Ethanol
S6003	PTC124 (Ataluren)	<1 mg/mL	57 mg/mL	<1 mg/mL
S1565	VX-809	<1 mg/mL	91 mg/mL	16 mg/mL
S1144	Ivacaftor (VX-770)	<1 mg/mL	79 mg/mL	<1 mg/mL
S7059	VX-661	<1 mg/mL	104 mg/mL	<1 mg/mL

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Product Categories

Ivacaftor (VX-770)

Validation & Quality Control

Product Citations(1)

Quality Control & MSDS

Related Compound Libraries

Ivacaftor (VX-770) is available in the following compound libraries:

Product Information

Compare CFTR Chemicals

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [1]

References

Chemical Information

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Product Citations (1)

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Kinase Assay: ^[1]