Ivacaftor (VX-770)

別名:VX-770

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)化学構造

CAS No. 873054-44-5

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 35500 国内在庫あり
JPY 25500 国内在庫あり
JPY 145500 国内在庫あり
JPY 208500 国内在庫あり
JPY 445500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール:[email protected]
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製品安全説明書

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Ivacaftor (VX-770)と併用されることが多い化合物

Tezacaftor (VX-661)


Tezacaftor specifically target F508del CFTR whereas, Ivacaftor targets both G551D-CFTR and F508del-CFTR.

Elexacaftor (VX-445)


Elexacaftor exhibits multiplicative synergy with Ivacaftor in potentiating Class III and IV CFTR mutations.

Shaughnessy CA, et al. Scientific reports 11.1 (2021): 19810.

Lumacaftor (VX-809)


Ivacaftor and Lumacaftor are used for the treatment of Cystic fibrosis (CF) in homozygous individuals for the F508del mutation.

Cheng PC, et al. Expert Rev Respir Med. 2019 May; 13(5): 417–423.

CFTRinh-172


Ivacaftor (VX-770) is a CFTR potentiator, whereas CFTRinh-172 is an CFTR inhibitor.

Laselva O, et al. Eur Respir J. 2021 Jun; 57(6): 2002774.

Icenticaftor (QBW251)


Ivacaftor and Icenticaftor are small-molecule channel potentiators of CFTR that are under clinical trials for their roles in chronic obstructive pulmonary disease.

Dransfield M, et al. American journal of respiratory and critical care medicine 205.6 (2022): 631-640.

Ivacaftor (VX-770)関連製品

シグナル伝達経路

CFTR阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
HBE  Function Assay 10 µM 24 h induces a modest but significant increase in ASL depth 22768130
HBE  Function Assay 10 μM 10 min augments CFTR-dependent ion transport  24106801
HBE  Function Assay 10 µM augments CFTR-dependent anion transport activity 22768130
CFBE41o- Function Assay 10 µM induces robust increases in anion transport 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 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
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
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 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
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
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生物活性

製品説明 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.
特性 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 (IT) 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 IT, Ivacaftor (10 μM) increases the open probability (Po) 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 IT 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 IT 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]

Kinase Assay Ussing Chamber Recordings
The effect of Ivacaftor on CFTR-mediated Cl- secretion is characterized by measuring the CFTR-mediated IT 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 IT in the voltage-clamp mode (Vhold = 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
細胞実験 細胞株 FRT and NIH 3T3 cells
濃度 100/25 nM
反応時間 24 h
実験の流れ

Cells were treated with various concentrations of VX-770.

実験結果図 Methods Biomarkers 結果図 PMID
Western blot PPARγ / pERK NLRP3 Rδf508 30498130
Immunofluorescence F-actin 30498130
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
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
NCT02724527 Unknown status
Cystic Fibrosis
Nivalis Therapeutics Inc.
April 2016 Phase 2

化学情報

分子量 392.49 化学式

C24H28N2O3

CAS No. 873054-44-5 SDF Download Ivacaftor (VX-770) SDFをダウンロードする
Smiles CC(C)(C)C1=CC(=C(C=C1NC(=O)C2=CNC3=CC=CC=C3C2=O)O)C(C)(C)C
保管

In vitro
Batch:

DMSO : 79 mg/mL ( (201.27 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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