VX-809 (Synonyms: VX 809; VX809; Lumacaftor; VRT 826809) |
| Catalog No.GC15455 |
VX-809 (VX-809; VRT 826809) is a CFTR modulator that corrects the folding and trafficking of CFTR protein.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 936727-05-8
Sample solution is provided at 25 µL, 10mM.
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VX-809 is a CFTR corrector that partially restores the function of F508del-CFTR. In Fischer rat thyroid (FRT) cells, it increases F508del-CFTR maturation at EC50 of 0.1 μM, and elevates F508del-CFTR–mediated chloride transport at EC50 of 0.5 μM [1]. It has no effect of other ion channels (hERG), transporter (P-gp) and disease-causing mislocalized proteins (α1-antitrypsin Z mutant) [1]. VX-809 stabilizes N-terminal fragment of CFTR that contain MSD1 by altering its protein conformation [2, 3].
Homozygous F508del-CFTR is the most common mutation in cystic fibrosis (CF) patients, accounting for 66–70% of CF cases worldwide. In cultured human bronchial epithelial cells that are homozygous for F508del, VX-809 restored the CFTR function and improved chloride and fluid Transport [1]. The combination of CFTR potentiators and VX-809 further improved the function of F508del-CFTR [4].
VX-809 has been tested in several clinical trials. Although it had minimal benefit to F508del-CFTR homozygous patients as a monotherapy [4], the result of Phase 2 study of VX-809 and KALYDECO combination showed significant improvements in lung function in CF patients with homozygous F508del-CFTR [5]. VX-809 is currently under investigation in two phase 3 trials.
References:
[1]Van Goor F, Hadida S, Grootenhuis PD et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A 2011; 108: 18843-18848.[2] Ren HY, Grove DE, De La Rosa O et al. VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1. Mol Biol Cell 2013; 24: 3016-3024.[3]Loo TW, Bartlett MC, Clarke DM. Corrector VX-809 stabilizes the first transmembrane domain of CFTR. Biochem Pharmacol 2013; 86: 612-619.[4]Clancy JP, Rowe SM, Accurso FJ et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax 2012; 67: 12-18.[5]http://investors.vrtx.com/releasedetail.cfm?releaseid=687394
| Kinase experiment [1]: | |
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Inhibitory activities |
Lumacaftor(VX-809), succeeded in a Phase III clinical trial, is a cystic fibrosis transmembrane conductance regulator (CFTR) corrector. VX-809 had been shown to increase membrane expression of mutant channels and cell surface density of functional F508del-CFTR in vitro. |
| Cell experiment [2]: | |
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Cell |
Human bronchial epithelial (HBE) cells, F508del-CFBE cells, CF-HBE cells (F508del/F508del) and A549 cells. |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
Expose time: 48 h. |
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Applications |
In human bronchial epithelial (HBE) cells, VX-809 could increase F508del-CFTR Cl secretion, and increase FEV1 by an average of 3-5% in CF patients with homozygous for the F508del-CFTR mutation in combination with VX-770. |
| Human experiment [1]: | |
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Patients model |
Patients with Cystic Fibrosis Homozygous |
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Dosage form |
600 mg once daily or 400 mg every 12 hours |
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Preparation method |
orally administered |
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Applications |
At the plasma membrane, it increased F508del-CFTR levels. Alone or in combination with ivacaftor improved clinical outcome in patients with homozygous for the F508del mutation, Lumacaftor acted an key role in the treatment of biochemical abnormalities in CF. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. The actual solubility may slightly differ with the theoretical value. |
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References: [1]. Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. [2] Stanton BA, Coutermarsh B, Barnaby R, et al. Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells. PLoS One. 2015 May 27;10(5) | |
| Cas No. | 936727-05-8 | SDF | |
| Synonyms | VX 809; VX809; Lumacaftor; VRT 826809 | ||
| Chemical Name | 3-[6-[[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl]amino]-3-methylpyridin-2-yl]benzoic acid | ||
| Canonical SMILES | CC1=C(N=C(C=C1)NC(=O)C2(CC2)C3=CC4=C(C=C3)OC(O4)(F)F)C5=CC(=CC=C5)C(=O)O | ||
| Formula | C24H18F2N2O5 | M.Wt | 452.41 |
| Solubility | ≥ 22.6mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 | 0.221 mL | 1.1052 mL | 2.2104 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 36 reference(s) in Google Scholar.)
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