VX-809 (Lumacaftor)

製品コードS1565 別名:VRT 826809

VX-809 (Lumacaftor)化学構造

分子量(MW):452.41

VX-809 (Lumacaftor) acts to correct CFTR mutations common in cystic fibrosis by increasing mutant CFTR (F508del-CFTR) maturation,EC50 of 0.1 μM in fisher rat thyroid cells. Phase 3.

サイズ 価格(税別)  
In DMSO JPY 58400
JPY 30200
JPY 55100
JPY 163000
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バルク問合せ

文献中Selleckの製品使用例(44)

製品安全説明書

CFTR阻害剤の選択性比較

生物活性

製品説明 VX-809 (Lumacaftor) acts to correct CFTR mutations common in cystic fibrosis by increasing mutant CFTR (F508del-CFTR) maturation,EC50 of 0.1 μM in fisher rat thyroid cells. Phase 3.
特性 Higher specificity and efficacy relative to other CFTR defect drugs.
ターゲット
F508del-CFTR [1]
(Fisher rat thyroid cells)
0.1 μM(EC50)
体外試験

VX-809 acts at the level of the ER to allow a fraction of the F508del-CFTR to adopt a properly folded form, to exit the ER and mobilize to the cell surface for normal functioning. In Fischer rat thyroid (FRT) cells expressing F508del-CFTR, VX-809 treatment significantly improves F508del-CFTR maturation by 7.1 fold with an EC50 of 0.1 μM, and enhances F508del-CFTR-mediated chloride transport by approximately 5 fold with EC50 of 0.5 μM, while VRT-768 has higher EC50 values of 7.9 μM and 16 μM, respectively. In HEK-293 cells expressing F508del-CFTR, VX-809 (3 μM) treatment increases F508del-CFTR exit from the ER by 6 fold, reaching levels comparable to 34% of CFTR. In primary human bronchial epithelial (HBE) cells with F508del-CFTR mutation, VX-809 increases CFTR maturation and enhances chloride secretion with EC50 of 350 nM and 81 nM, respectively, more efficacious than Corr-4a and VRT-325. F508del-CFTR corrected by VX-809 exhibits single-channel open probability of 0.39 similar to normal CFTR of 0.40. Unlike VX-770, VX-809 is not a CFTR potentiator, as acute addition of VX-809 has no effect on F508del-CFTR function. In contrast to VRT-325 and Corr-4a, VX-809 does not improve the processing of the normal or mutant forms of hERG or P-gp, as well as other disease-causing mislocalized proteins, including α1-antitrypsin Z mutant (E342K-α1-AT) or N370S-β-glucosidase, suggesting that VX-809 is specific for CFTR. VX-809 in combination with VRT-325 or Corr-4a has additive effect on CFTR-mediated chloride transport in cultured F508del-HBE. [1]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human CFBE41o cells MmrnSpVv[3Srb36gZZN{[Xl? NFexbo1Ed3K{ZXP0c5Ih[WO2aY\peJkh[XRiQ1\UVkBHPTB6ZHXsJI12fGGwdDCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBpfW2jbjDDSmJGPDGxIHPlcIx{KGG|c3Xzd4VlKGG|IHnuZ5Jm[XOnIHnuJIZ2dGy7IHfsfYNwe3muYYTl[EBxem:2ZXnuJIJ6KHenc4Tldo4h[myxdDDhcoFtgXOrcx?= M3vqTVI3ODRzNUe3

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アッセイ
Methods Test Index PMID
Immunofluorescence
CFTR / USP13; 

PubMed: 30618756     


Confocal microscope images taken from CFBE41o- cells stained with antibodies against CFTR and USP13. Cells were treated with VX-809 (1 μM) or vehicle. Arrows indicate examples of cells with peripheral co-localization of F508del-CFTR and USP13. Arrowheads show peripheral regions with USP13 alone. Insets depict magnified cell areas of cell periphery with colocalization of USP13 and F508del-CFTR.

Cell surface kAE1 / kAE1; 

PubMed: 23460825     


MDCK cells expressing WT or kAE1 mutant were either kept in control conditions or treated with 3 µM of the molecular chaperone VX-809 for 24 hours prior to fixation. We then performed a two-step immunostaining as follows: cells were blocked and stained with a mouse anti-HA antibody followed by staining with an Alexa 488 coupled secondary antibody. Cells were then permeabilized and after blocking, stained again with a mouse anti-HA antibody followed by a Cy3 coupled secondary antibody. The samples were examined with a WaveFx spinning disk using a 60×oil immersion objective. The size bar corresponds to 10 µm

30618756 23460825

お薦めの試験操作(参考用のみ)

キナーゼ試験:[1]
+ 展開

F508del-CFTR maturation:

Fischer rat thyroid (FRT) cells stably expressing F508del-CFTR are treated with increasing concentrations of VX-809 for 48 hours. After incubation, cells are harvested in ice-cold D-PBS solution (without calcium and magnesium) and pelleted at 1,000 × g at 4 °C. Cell pellets are lysed in 1% Nonidet P-40, 0.5% sodium deoxycholate, 200 mM NaCl, 10 mM Tris, pH 7.8, and 1 mM EDTA plus protease inhibitor mixture (1:250) for 30 minutes on ice. Lysates are spun for 10 minutes at 10,000 × g at 4 °C to pellet nuclei and insoluble material. Approximately 12 μg total protein is heated in Laemmli buffer with 5% β-mercaptoethanol at 37 °C for 5 minutes and loaded onto a 3% to 8% Tris-acetate gel. The gel is transferred to nitrocellulose and processed for Western blotting by using monoclonal CFTR antibody or polyclonal to GAPDH. Blots are developed by enhanced chemiluminescence. Quantification of the relative amounts of bands C and GAPDH is performed by using NIH ImageJ analysis of scanned films.
細胞試験: [1]
+ 展開
  • 細胞株: FRT (CFTR or F508del-CFTR), HEK-293 (CFTT or F508del-CFTR) , and HBE cells
  • 濃度: Dissolved in DMSO, final concentrations ~0.1 mM
  • 反応時間: 24 or 48 hours
  • 実験の流れ: Cells are exposed to various concentrations of VX-809 for 24 or 48 hours. Ussing chamber techniques are used to record the transepithelial current (IT) resulting from CFTR-mediated chloride transport. The single-channel activity of CFTR is measured by using excised inside-out membrane patch recordings. Immunoblot techniques using themonoclonal CFTR antibody are used to measure CFTR maturation in FRT, HEK-293, or HBE cells expressing CFTR or F508del-CFTR.
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 90 mg/mL (198.93 mM)
Ethanol 6 mg/mL (13.26 mM)
Water Insoluble
体内 左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
30% PEG400+0.5% Tween80+5% propylene glycol
混合させたのち直ちに使用することを推奨します。
30 mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報

分子量 452.41
化学式

C24H18F2N2O5

CAS No. 936727-05-8
保管
in solvent
別名 VRT 826809

便利ツール

モル濃度計算器

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • 質量
    濃度
    体積
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03512119 Recruiting Cystic Fibrosis Homozygous for Phe 508 Del CFTR|Glucose Intolerance or Newly Diagnosis Diabetes University Hospital Strasbourg France February 11 2016 --
NCT02589236 Completed Cystic Fibrosis Nivalis Therapeutics Inc.|Medidata Solutions November 2015 Phase 2
NCT02544451 Active not recruiting Cystic Fibrosis Vertex Pharmaceuticals Incorporated August 2015 Phase 3
NCT02514473 Completed Cystic Fibrosis Vertex Pharmaceuticals Incorporated July 2015 Phase 3

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Handling Instructions

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  • * 必須

CFTRシグナル伝達経路

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID