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Reagents and instruments for immunology, cell biology and molecular biology.

Ivacaftor [873054-44-5]

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Cat# HY-13017-5mg

Size : 5mg

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Phone : +1 850 650 7790

Brand : MedChemExpress

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Phone : +1 850 650 7790

Description

Ivacaftor (VX-770) is a potent and orally bioavailable CFTR potentiator, targeting G551D-CFTR and F508del-CFTR with EC₅₀s of 100 nM and 25 nM, respectively.

IC₅₀ & Target

EC50: 100 nM (G551D-CFTR), 25 nM (F508del-CFTR)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
Epithelial cell	EC₅₀	0.236 μM Compound: 48	Potentiation of human CFTR F508del mutant in human bronchial epithelial cells by Ussing chambers recording technique Potentiation of human CFTR F508del mutant in human bronchial epithelial cells by Ussing chambers recording technique	[PMID: 25441013]
Epithelial cell	EC₅₀	22 nM Compound: 48	Potentiation of human CFTR F508del/G551D mutant in human bronchial epithelial cells by Ussing chambers recording technique Potentiation of human CFTR F508del/G551D mutant in human bronchial epithelial cells by Ussing chambers recording technique	[PMID: 25441013]
NIH3T3	EC₅₀	3 nM Compound: 48	Potentiation of human CFTR F508del mutant expressed in mouse NIH-3T3 cells after 30 mins by fluorescent voltage sensing optical assay Potentiation of human CFTR F508del mutant expressed in mouse NIH-3T3 cells after 30 mins by fluorescent voltage sensing optical assay	[PMID: 25441013]
Vero	CC₅₀	27.34 μM Compound: Ivacaftor	Cell viability measured by CellTiter-Glo assay in Vero cells at MOI 0.05 after 72hr Cell viability measured by CellTiter-Glo assay in Vero cells at MOI 0.05 after 72hr	10.1101/2020.03.20.999730
Vero	IC₅₀	6.57 μM Compound: Ivacaftor	Antiviral activity against SARS-CoV-2 (viral titer) measured by plaque assay in Vero cells at MOI 0.0125 after 24 hr Antiviral activity against SARS-CoV-2 (viral titer) measured by plaque assay in Vero cells at MOI 0.0125 after 24 hr	10.1101/2020.03.20.999730

In Vitro

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].

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

In Vivo

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.

Clinical Trial

Molecular Weight

392.49

Formula

C₂₄H₂₈N₂O₃

CAS No.

873054-44-5

Appearance

Solid

Color

White to off-white

SMILES

CC(C)(C1=C(C=C(C(C(C)(C)C)=C1)O)NC(C2=CNC3=C(C2=O)C=CC=C3)=O)C

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Solvent & Solubility

In Vitro:

DMSO : 50 mg/mL (127.39 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.5478 mL	12.7392 mL	25.4784 mL
5 mM	0.5096 mL	2.5478 mL	5.0957 mL
10 mM	0.2548 mL	1.2739 mL	2.5478 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.37 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.37 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 3

Add each solvent one by one: 5% DMSO 95% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (6.37 mM); Suspended solution; Need ultrasonic

Purity & Documentation

Purity: 99.90%

Data Sheet (277 KB) SDS (393 KB)

COA (249 KB) LCMS (268 KB)

Handling Instructions (2659 KB)

References

[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]

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Cat# HY-13017-5mg

Contact local distributor :

Brand : MedChemExpress

Contact local distributor :

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