Ivacaftor (VX-770)

카탈로그 번호S1144 배치:S114404

인쇄

기술 자료

화학식

C24H28N2O3
분자량 392.49 CAS 번호 873054-44-5
용해도 (25°C)* 시험관 내(In vitro) DMSO 78 mg/mL (198.73 mM)
Water Insoluble
Ethanol Insoluble
생체 내(In Vivo) (개별적으로 순서대로 용매를 제품에 첨가하십시오.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml은 약간 용해되거나 불용해됨을 의미합니다.
* Selleck은 모든 화합물의 용해도를 자체적으로 테스트하며, 실제 용해도는 게시된 값과 약간 다를 수 있습니다. 이는 정상적인 현상이며, 약간의 배치 간 변동으로 인해 발생합니다.
* 실온 배송 (안정성 테스트 결과 이 제품은 냉각 조치 없이 배송될 수 있음을 보여줍니다.)

원액 준비

생물학적 활성

설명 Ivacaftor (VX-770)은 G551D-CFTR 및 F508del-CFTR을 표적으로 하는 CFTR의 선택적 증강제이며, fisher rat thyroid 세포에서 각각 100 nM 및 25 nM의 EC50을 나타냅니다.
표적
F508del-CFTR
(Fisher rat thyroid cells)		 G551D-CFTR
(Fisher rat thyroid cells)
25 nM(EC50) 100 nM(EC50)
시험관 내(In vitro)

Ivacaftor (VX-770) (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, this compound increases the open probability (Po) of G551D-, F508del-, and wild-type CFTR by ~6-fold, ~5-fold and ~2-fold, respectively, indicating that it 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 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, it 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, this compound 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.

특징 인체 임상 시험에 진입한 최초의 강력하고 경구 투여 가능한 CFTR potentiator.

프로토콜 (참조)

키나아제 분석:

[1]
  • Ussing Chamber 기록

    Ivacaftor (VX-770)가 CFTR 매개 Cl- 분비에 미치는 영향은 G551D 또는 F508del CFTR을 발현하는 재조합 Fisher rat thyroid(FRT) 세포를 사용하여 챔버에서 CFTR 매개 IT를 측정함으로써 특징지어집니다. 세포는 기록 전 37°C에서 유지되는 Costar Snapwell 세포 배양 인서트에서 배양됩니다. 세포 배양 인서트를 Ussing 챔버에 장착하여 전압 클램프 모드(Vhold = 0 mV)에서 IT를 기록합니다. FRT 세포의 경우, 기저측막(basolateral membrane)에서 기저측(basolateral)에서 정점(apical)으로의 Cl- 구배가 설정됩니다. 기저측 욕액(basolateral bath solution)은 135 mM NaCl, 1.2 mM CaCl2, 1.2 mM MgCl2, 2.4 mM K2HPO4, 0.6 mM KHPO4, 10 mM N-2-hydroxyethylpiperazine-N을 포함합니다.
세포 분석:

[2]
  • 세포주

    FRT and NIH 3T3 cells

  • 농도

    100/25 nM

  • 배양 시간

    24 h

  • 방법

    Cells were treated with various concentrations of Ivacaftor (VX-770).
동물 연구:

[2]
  • 동물 모델

    Male Sprague-Dawley rats

  • 용량

    3 mg/kg

  • 투여

    i.v.

참조

  • https://pubmed.ncbi.nlm.nih.gov/19846789/
  • https://pubmed.ncbi.nlm.nih.gov/25441013/

고객 제품 검증

(A) CFTR Western blot of normal (NL) and CF HBE cultures treated with VX-809 (5 uM) ± VX-770 (5 uM) for 48 hours. “*” indicates the mature, complex glycosylated form of CFTR, band C; “•” indicates the immature band B. (B) Turnover of rescued ΔF508 in BHK-21 cells. ΔF508 was rescued at 27°C in the presence of VX-809 ± VX-770 for 24 hours. After adding cycloheximide (200 ug/ml, 37°C), cells were lysed at the indicated times and analyzed by Western blotting.

데이터 출처 [ Sci Transl Med , 2014 , 6(246), 246ra96 ]

<p> </p><p>(A) Representative traces of Ca2+ mobilization induced by 100 μm of OAG after modulation of CFTR activity with 10 μm VX-770. (B) Histograms show normalized AUC corresponding to Ca2+ mobilization induced by 100 μm OAG (n, number of cells recorded/N, number of cell passages).</p>

,

<p> </p><p>(C) Representative traces of iodide efflux curves after CFTR stimulation with 10 μm VX-770 or 100μm OAG. (D) Histograms show the mean relative rate of CFTR activity for the experimental condition indicated below each bar (n = 4).</p>

,

Treatment with DF508 CFTR correcting drugs (VX-770 and VX-809, 10 lM) partially redistributed F-actin in the submembrane compartment as also shown by the two small membrane peaks in the quantification graph. Treatment with PP2 (1 lM) alone or in combination with VX-770 and VX-809 completely recovered the actin distribution in DF508-chol similar to Control-chol. Phalloidin fluorescence intensity confirms the presence of membrane sharper peaks that reach intensity values comparable to Control-chol. Abbreviations: A.U, arbitrary units; chol, cholangiocytes.

데이터 출처 [ , , Hepatology, 2018, 67(3):972-988 ]

Selleck's Ivacaftor (VX-770) 인용됨 298 출판물

Identification of small molecules that enhance aminoglycoside-mediated suppression of CFTR and NF1 nonsense mutations [ Mol Ther Oncol, 2026, 34(2):201173] PubMed: 41939791
Altered functional interactions between CFTR disease mutants ΔF508 and G551D and the protein kinase A catalytic subunit [ J Physiol, 2026, 604(8):3344-3362] PubMed: 41920076
Investigation of HE4 expression concerning epithelial-mesenchymal transition (EMT) in cystic fibrosis epithelial cells [ J Cyst Fibros, 2026, S1569-1993(26)00086-X] PubMed: 41936498
Functional, Cohort-Level Assessment of CFTR Modulator Responses Using Biobanked Nasal Epithelial Cells from Individuals with Cystic Fibrosis [ J Pers Med, 2026, 16(1)51] PubMed: 41590543
CFTR rescue in W1282X cystic fibrosis patient-derived intestinal organoids (PDIOs) mediated by translational readthrough-inducing drugs (TRIDs) [ Genet Med Open, 2026, 4:103472] PubMed: 41492359
ACE-tRNAs are a platform technology for suppressing nonsense mutations that cause cystic fibrosis [ Nucleic Acids Res, 2025, 53(13)gkaf675] PubMed: 40650978
Transcriptomic and functional responses of the cystic fibrosis airway epithelium to CFTR modulator therapy [ JCI Insight, 2025, 10(21)e196018] PubMed: 41212059
Endometrium-derived organoids from cystic fibrosis patients and mice as new models to study disease-associated endometrial pathobiology [ Cell Mol Life Sci, 2025, 82(1):109] PubMed: 40074868
CFTR negatively reprograms Th2 cell responses, and CFTR potentiation restrains allergic airway inflammation [ JCI Insight, 2025, 10(9)e191098] PubMed: 40131363
Human induced pluripotent stem cells for in vitro modeling of impaired mucociliary clearance in cystic fibrosis lung disease [ Stem Cell Res Ther, 2025, 16(1):573] PubMed: 41116195

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