VX-809 (Lumacaftor)

Catalog No.S1565 Synonyms: VRT 826809

VX-809 (Lumacaftor) Chemical Structure

Molecular Weight(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.

Size Price Stock Quantity  
In DMSO USD 340 In stock
USD 170 In stock
USD 320 In stock
USD 970 In stock
Bulk Discount

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

Cited by 44 Publications

Purity & Quality Control

Choose Selective CFTR Inhibitors

Biological Activity

Description 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.
Features Higher specificity and efficacy relative to other CFTR defect drugs.
Targets
F508del-CFTR [1]
(Fisher rat thyroid cells)
0.1 μM(EC50)
In vitro

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human CFBE41o cells MXrGeY5kfGmxbjDhd5NigQ>? Mn\HR49zemWldH;yJIFkfGm4aYT5JIF1KEOIVGKgSlUxQGSnbDDteZRidnRiKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gbJVu[W5iQ1\CSVQydyClZXzsd{Bie3Onc4Pl[EBieyCrbnPy[YF{\SCrbjDmeYxtgSCpbInjc5N6dGG2ZXSgdJJwfGWrbjDifUB4\XO2ZYLuJIJtd3RiYX7hcJl{cXN? MoLuNlYxPDF3N{e=

... Click to View More Cell Line Experimental Data

Assay
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

Protocol

Kinase Assay:[1]
+ Expand

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.
Cell Research:[1]
+ Expand
  • Cell lines: FRT (CFTR or F508del-CFTR), HEK-293 (CFTT or F508del-CFTR) , and HBE cells
  • Concentrations: Dissolved in DMSO, final concentrations ~0.1 mM
  • Incubation Time: 24 or 48 hours
  • Method: 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.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 90 mg/mL (198.93 mM)
Ethanol 6 mg/mL (13.26 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
30 mg/mL

* 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.

Chemical Information

Molecular Weight 452.41
Formula

C24H18F2N2O5

CAS No. 936727-05-8
Storage powder
in solvent
Synonyms VRT 826809

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • 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):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03512119 Recruiting Drug: Lumacaftor-Ivacaftor treatment Cystic Fibrosis Homozygous for Phe 508 Del CFTR|Glucose Intolerance or Newly Diagnosis Diabetes University Hospital Strasbourg France February 11 2016 --
NCT02589236 Completed Drug: Cavosonstat|Drug: Placebo Cystic Fibrosis Nivalis Therapeutics Inc.|Medidata Solutions November 2015 Phase 2
NCT02544451 Active not recruiting Drug: Ivacaftor|Drug: Lumacaftor Cystic Fibrosis Vertex Pharmaceuticals Incorporated August 2015 Phase 3
NCT02514473 Completed Drug: VX-809|Drug: Placebo|Drug: VX-770 Cystic Fibrosis Vertex Pharmaceuticals Incorporated July 2015 Phase 3
NCT01899105 Completed Drug: lumacaftor|Drug: ivacaftor Cystic Fibrosis Vertex Pharmaceuticals Incorporated July 2013 Phase 1
NCT01897233 Completed Drug: Lumacaftor|Drug: Ivacaftor Cystic Fibrosis Vertex Pharmaceuticals Incorporated July 2013 Phase 3

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

CFTR Signaling Pathway Map

Related CFTR Products

Tags: buy VX-809 (Lumacaftor) | VX-809 (Lumacaftor) supplier | purchase VX-809 (Lumacaftor) | VX-809 (Lumacaftor) cost | VX-809 (Lumacaftor) manufacturer | order VX-809 (Lumacaftor) | VX-809 (Lumacaftor) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID