1. Membrane Transporter/Ion Channel
  2. CFTR

VX-809 (Synonyms: Lumacaftor; VRT 826809)

Cat. No.: HY-13262 Purity: 99.12%
Handling Instructions

VX-809 is a CFTR modulator that corrects the folding and trafficking of CFTR protein.

For research use only. We do not sell to patients.

VX-809 Chemical Structure

VX-809 Chemical Structure

CAS No. : 936727-05-8

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 132 In-stock
Estimated Time of Arrival: December 31
5 mg USD 120 In-stock
Estimated Time of Arrival: December 31
10 mg USD 180 In-stock
Estimated Time of Arrival: December 31
50 mg USD 540 In-stock
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100 mg USD 780 In-stock
Estimated Time of Arrival: December 31
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    VX-809 purchased from MCE. Usage Cited in: J Physiol Sci. 2018 Jun 27.

    Effect of VX-809 on maturation of Δ(G970-T1122)-CFTR protein. Immunoblots for WT-, ΔF508-, and Δ(G970-T1122)-CFTR proteins expressed in CHO cells in the presence of 0, 3, or 10 μM VX-809 at a 37°C for 24 h or b 27°C for 48 h.

    VX-809 purchased from MCE. Usage Cited in: Sci Rep. 2015 Oct 30;5:15946.

    VX-809 reverses the heat-induced effects in cells including reduction in CFTR, upregulation of COX-2 and increases in PGE2.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    VX-809 is a CFTR modulator that corrects the folding and trafficking of CFTR protein.

    IC50 & Target

    EC50: 0.1 μM (CFTR)[1]

    In Vitro

    In fischer rat thyroid (FRT) cells, VX-809 improves F508del-CFTR maturation by 7.1±0.3 fold (n=3) compared with vehicle-treated cells (EC50, 0.1±0.1 μM; n=3) and enhances F508del-CFTR-mediated chloride transport by approximately fivefold (EC50, 0.5±0.1 μM; n=3). At VX-809 concentrations greater than 10 μM, the response is reduced, resulting in a bell-shaped dose-response relationship with an IC50 of approximately 100 μM. VX-809 is orally bioavailable in rats and achieved in vivo plasma levels significantly above concentrations required for in vitro efficacy[1]. VX-809 produces a concentration-dependent increase in the HRP luminescence signal after incubation with cells at 37°C or 27°C in both cell lines, with a similar EC50 value of approximately 0.3 µM. In F508-HRP CFBE41o- cells at 37°C, VX-809 increases the signal maximally to approximately 250 luminescence arbitrary units (a.u.) over the DMSO control baseline of approximately 60 a.u., representing an approximately 4-fold signal increase. Similarly, with the R1070W-HRP CFBE41o- cells, VX-809 increases the signal maximally to approximately 220 a.u. over the DMSO control baseline of approximately 85 a.u., representing an approximately 2.5-fold signal increase. Therefore, both cell lines produced robust signals with a good dynamic range for high-throughput screening[2].

    In Vivo

    Oral dosing of 1 mg/kg VX-809 in male Sprague-Dawley rats results in a Cmax of 2.4±1.3 μM with a t1/2 of 7.7±0.4 h (mean±SD; n=3), indicating that that VX-809 is orally bioavailable and able to reach plasma levels that significantly exceeded EC50s for F508del-CFTR correction[1].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    10 mM in DMSO

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.2104 mL 11.0519 mL 22.1038 mL
    5 mM 0.4421 mL 2.2104 mL 4.4208 mL
    10 mM 0.2210 mL 1.1052 mL 2.2104 mL
    *Please refer to the solubility information to select the appropriate solvent.
    References
    Kinase Assay
    [2]

    Screening is carried out using a Beckman Coulter Biomek FX platform. In one set of assays, R1070W-F508-CFTR-HRP (R1070W-HRP)-expressing CFBE41o- cells are incubated with 100 µL medium containing 25 µM test compounds and 0.5 μg/mL Doxycycline for 24 hours at 37°C. In a second set of assays, F508-CFTR-HRP (F508-HRP)-expressing CFBE41o- cells are incubated with 100 µL medium containing 25 µM test compounds, 2 µM VX-809, and 0.5 μg/mL doxycycline for 24 hours at 37°C. All compound plates contain negative controls (DMSO) and positive controls (2 µM VX-809). In both assays, the cells are washed four times with PBS, and HRP activity is assayed by the addition of 50 µL/well of HRP substrate. After shaking for 5 minutes, chemiluminescence is measured using a Tecan Infinite M1000 plate reader equipped with an automated stacker (integration time, 100 milliseconds)[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    .A549 cells expressing F508-CFTR YFP are grown at 37°C/5% CO2 for 18-24 hours after plating. The cells are then incubated with 100 μL of medium containing test compounds for 18-24 hours. At the time of the assay, cells are washed with PBS and then incubated for 10 minutes with PBS containing forskolin (20 μM) and genistein (50 μM). Each well is assayed individually for I- influx by recording fluorescence continuously (200 milliseconds per point) for 2 seconds (baseline) and then for 12 seconds after rapid addition of 165 μL PBS in which 137 mM Cl- is replaced by I-. The initial I- influx rate is computed by fitting the final 11.5 seconds of the data to an exponential for extrapolation of initial slope, which is normalized for background-subtracted initial fluorescence. All compound plates contain negative controls (DMSO vehicle) and positive controls (5 µM VX-809). Fluorescence is measured using a Tecan Infinite M1000 plate reader equipped with a dual syringe pump (excitation/emission 500/535 nm)[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Rats[1]
    Male rats (n=3 per dose group) are orally administered VX-809 in a vehicle consisting of 0.5% Tween80/0.5% methylcellulose/water at a dose volume of 5 mL/kg. The concentration of VX-809 in plasma samples is determined with a liquid chromatography/tandem MS method. Pharmacokinetic parameters are calculated byusing WinNonlin Professional Edition software, version 4.0.1..

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    452.41

    Formula

    C₂₄H₁₈F₂N₂O₅

    CAS No.

    936727-05-8

    SMILES

    FC1(F)OC(C=C(C=C2)C3(CC3)C(NC4=NC(C5=CC=CC(C(O)=O)=C5)=C(C=C4)C)=O)=C2O1

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.12%

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    Product Name:
    VX-809
    Cat. No.:
    HY-13262
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    VX-809

    Cat. No.: HY-13262