Ivacaftor (VX-770)

製品コードS1144 バッチS114402

印刷

化学情報

Chemical Structure Synonyms VX-770 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H28N2O3
分子量 392.49 CAS No. 873054-44-5
Solubility (25°C)* 体外 DMSO 79 mg/mL (201.27 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

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

プロトコル(参考用のみ)

キナーゼアッセイ 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
細胞アッセイ 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.
動物実験 動物モデル Male Sprague-Dawley rats
投薬量 3 mg/kg
投与方法 i.v.

カスタマーフィードバック

Data from [Data independently produced by Sci Transl Med, 2014, 6(246), 246ra96]

,

,

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Comprehensive Assessment of CFTR Modulators' Therapeutic Efficiency for N1303K Variant [ Int J Mol Sci, 2024, 25(5)2770] PubMed: 38474016
PTI-801 (posenacaftor) shares a common mechanism with VX-445 (elexacaftor) to rescue p.Phe508del-CFTR [ Eur J Pharmacol, 2024, 967:176390] PubMed: 38336013
CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants [ Pancreatology, 2024, S1424-3903(24)00066-8] PubMed: 38493004
Functional rescue of CFTR in rectal organoids from patients carrying R334W variant by CFTR modulators and PDE4 inhibitor Roflumilast [ Respir Investig, 2024, 62(3):455-461] PubMed: 38547757
Single-Stranded DNA with Internal Base Modifications Mediates Highly Efficient Gene Insertion in Primary Cells [ bioRxiv, 2024, 2024.02.01.578476] PubMed: 38352420
TLN468 changes the pattern of tRNA used to read through premature termination codons in CFTR [ bioRxiv, 2024, 10.1101/2023.02.02.526440] PubMed: none
Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection [ J Clin Invest, 2023, 10.1172/JCI163402] PubMed: 37581936
Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection [ J Clin Invest, 2023, 133(19)e163402] PubMed: 37581936
The cystic fibrosis treatment Trikafta affects the growth, viability, and cell wall of Aspergillus fumigatus biofilms [ mBio, 2023, 14(5):e0151623] PubMed: 37830825
Olive Leaf Extract (OLE) as a Novel Antioxidant That Ameliorates the Inflammatory Response in Cystic Fibrosis [ Cells, 2023, 12(13)1764] PubMed: 37443798

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。