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Ivacaftor (VX-770)

Name: Ivacaftor (VX-770)
Brand: Selleck Chemicals
SKU: S1144
Rating: 5 (246 reviews)

Synonyms: VX-770

Catalog No.S1144 Purity:99.97%

Ivacaftor (VX-770) is a selective potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM in fisher rat thyroid cells, respectively.

Ivacaftor (VX-770) Chemical Structure

CAS No. 873054-44-5

Purity & Quality Control

Batch: Purity: 99.97%

99.97

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Signaling Pathway

CFTR Signaling Pathway

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
HBE	Function Assay	10 μM	10 min	augments CFTR-dependent ion transport	24106801
CFBE41o-	Function Assay	10 µM		induces robust increases in anion transport	22768130
HBE	Function Assay	10 µM		augments CFTR-dependent anion transport activity	22768130
HBE	Function Assay	10 µM	24 h	induces a modest but significant increase in ASL depth	22768130
HBE	Function Assay	10 µM		potentiates CFTR-dependent Isc, regardless of prior administration of CSE	22768130
HBE	Function Assay	10 µM		partially restores depletion of ASL depth in CSE treated monolayers	22768130
mouse NIH-3T3 cells	Function assay		30 mins	Potentiation of human CFTR F508del mutant expressed in mouse NIH-3T3 cells after 30 mins by fluorescent voltage sensing optical assay, EC50 = 0.003 μM.	25441013
human bronchial epithelial cells	Function assay			Potentiation of human CFTR F508del/G551D mutant in human bronchial epithelial cells by Ussing chambers recording technique, EC50 = 0.022 μM.	25441013
human CFBE41o cells	Function assay		10 mins	Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay, EC50 = 0.126 μM.	29148763
human bronchial epithelial cells	Function assay			Potentiation of human CFTR F508del mutant in human bronchial epithelial cells by Ussing chambers recording technique, EC50 = 0.236 μM.	25441013
HEK293 cells	Function assay		10 mins	Potentiation of CFTR G551D mutant (unknown origin) expressed in HEK293 cells incubated for 10 mins in presence of forskolin measured for 2 mins by YFP halide assay, EC50 = 1.3 μM.	29148763
NRK-49F cells	Function assay			Inhibition of TGF-beta1-induced total collagen accumulation in rat NRK-49F cells, IC50 = 4 μM.	25467157
DAOY cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
NB-EBc1 cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
MG 63 (6-TG R) cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
RD cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
SK-N-MC cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
Saos-2 cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description

Ivacaftor (VX-770) is a selective potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM in fisher rat thyroid cells, respectively.

Features

The first potent and orally available CFTR potentiator to enter human clinical trials.

Targets

F508del-CFTR ^[1] (Fisher rat thyroid cells)	G551D-CFTR ^[1] (Fisher rat thyroid cells)
25 nM(EC50)	100 nM(EC50)

In vitro
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 response, resulting in an increase in the surface fluid and cilia beat frequency (CBF) in G551D/F508del HBE. ^[1]
Kinase Assay	Ussing Chamber Recordings
Kinase Assay	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 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
Cell Research	Cell lines	FRT and NIH 3T3 cells
	Concentrations	100/25 nM
	Incubation Time	24 h
	Method	Cells were treated with various concentrations of VX-770.
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	PPARγ / pERK NLRP3 Rδf508		30498130
	Immunofluorescence	F-actin		30498130

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT06331000	Not yet recruiting	Cystic Fibrosis	University Hospital Strasbourg France	March 2024	--
NCT05519020	Recruiting	Cystic Fibrosis	Sheffield Teaching Hospitals NHS Foundation Trust	July 27 2022	--
NCT04254705	Withdrawn	Cystic Fibrosis	Universitaire Ziekenhuizen KU Leuven\|Vertex Pharmaceuticals Incorporated\|KU Leuven\|University of Lisbon	March 1 2020	Not Applicable
NCT03085485	Completed	Chronic Obstructive Pulmonary Disease\|Chronic Bronchitis	University of Alabama at Birmingham\|National Heart Lung and Blood Institute (NHLBI)\|Vertex Pharmaceuticals Incorporated	March 16 2017	Phase 2

References

Chemical Information & Solubility

Molecular Weight	392.49	Formula	C₂₄H₂₈N₂O₃
CAS No.	873054-44-5	SDF	Download Ivacaftor (VX-770) SDF
Smiles	CC(C)(C)C1=CC(=C(C=C1NC(=O)C2=CNC3=CC=CC=C3C2=O)O)C(C)(C)C
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 79 mg/mL ( (201.27 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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Tech Support

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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