Ivacaftor (VX-770)

製品コードS1144 バッチS114404

化学情報

	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	78 mg/mL (198.73 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 (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]
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
キナーゼアッセイ	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
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.

参考

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]

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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：

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
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
Olive Leaf Extract (OLE) as a Novel Antioxidant That Ameliorates the Inflammatory Response in Cystic Fibrosis [ Cells, 2023, 12(13)1764]	PubMed: 37443798
Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis [ Int J Mol Sci, 2023, 24(7)6351]	PubMed: 37047318
Putting bicarbonate on the spot: pharmacological insights for CFTR correction in the airway epithelium [ Front Pharmacol, 2023, 14:1293578]	PubMed: 38149052
Theratyping of the Rare CFTR Genotype A559T in Rectal Organoids and Nasal Cells Reveals a Relevant Response to Elexacaftor (VX-445) and Tezacaftor (VX-661) Combination [ Int J Mol Sci, 2023, 24(12)10358]	PubMed: 37373505

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。

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