For research use only. Not for therapeutic Use.
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VX-809 acts to correct CFTR mutations common in cystic fibrosis by increasing mutant CFTR (F508del-CFTR) maturation,EC50 of 0.1 μM.
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<p>
VX-809 is the second investigational oral candidate compound for the treatment of cystic fibrosis (CF). VX-809 may act to restore the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, the defective cell membrane protein responsible for the progression of CF. VX-809 defects in the CFTR protein affect the transport of chloride and other ions across cells, and lead to the accumulation of thick, sticky mucus in the lungs of patients with CF. This mucus fosters chronic infection and inflammation, and results in irreversible lung damage.
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| Catalog Number | I005566 |
| CAS Number | 936727-05-8 |
| Synonyms | VX809;VX 809 |
| Molecular Formula | C24H18F2N2O5 |
| Purity | ≥95% |
| Target | CFTR |
| Solubility | 10 mM in DMSO |
| Storage | 3 years -20C powder |
| IC50 | 0.1 uM (EC50) |
| InChI | InChI=1S/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31) |
| InChIKey | UFSKUSARDNFIRC-UHFFFAOYSA-N |
| SMILES | OC(C1=CC(C2=C(C)C=CC(NC(C3(CC3)C4=CC(OC(F)(F)O5)=C5C=C4)=O)=N2)=CC=C1)=O |
| Reference | </br>1:Corrector VX-809 promotes interactions between cytoplasmic loop one and the first nucleotide-binding domain of CFTR. Loo TW, Clarke DM.Biochem Pharmacol. 2017 Mar 31. pii: S0006-2952(17)30182-X. doi: 10.1016/j.bcp.2017.03.020. [Epub ahead of print] PMID: 28366727 </br>2:Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770. Gentzsch M, Ren HY, Houck SA, Quinney NL, Cholon DM, Sopha P, Chaudhry IG, Das J, Dokholyan NV, Randell SH, Cyr DM.Am J Physiol Lung Cell Mol Physiol. 2016 Sep 1;311(3):L550-9. doi: 10.1152/ajplung.00186.2016. Epub 2016 Jul 8. PMID: 27402691 </br>3:Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR. Farinha CM, Sousa M, Canato S, Schmidt A, Uliyakina I, Amaral MD.Pharmacol Res Perspect. 2015 Aug;3(4):e00152. doi: 10.1002/prp2.152. Epub 2015 Jun 11. PMID: 26171232 Free PMC Article</br>4:Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells. Stanton BA, Coutermarsh B, Barnaby R, Hogan D.PLoS One. 2015 May 27;10(5):e0127742. doi: 10.1371/journal.pone.0127742. eCollection 2015. PMID: 26018799 Free PMC Article</br>5:Combined effects of VX-770 and VX-809 on several functional abnormalities of F508del-CFTR channels. Kopeikin Z, Yuksek Z, Yang HY, Bompadre SG.J Cyst Fibros. 2014 Sep;13(5):508-14. doi: 10.1016/j.jcf.2014.04.003. Epub 2014 May 3. PMID: 24796242 Free Article</br>6:Synergy-based small-molecule screen using a human lung epithelial cell line yields ΔF508-CFTR correctors that augment VX-809 maximal efficacy. Phuan PW, Veit G, Tan J, Roldan A, Finkbeiner WE, Lukacs GL, Verkman AS.Mol Pharmacol. 2014 Jul;86(1):42-51. doi: 10.1124/mol.114.092478. Epub 2014 Apr 15. PMID: 24737137 Free PMC Article</br>7:VX-809 and related corrector compounds exhibit secondary activity stabilizing active F508del-CFTR after its partial rescue to the cell surface. Eckford PD, Ramjeesingh M, Molinski S, Pasyk S, Dekkers JF, Li C, Ahmadi S, Ip W, Chung TE, Du K, Yeger H, Beekman J, Gonska T, Bear CE.Chem Biol. 2014 May 22;21(5):666-78. doi: 10.1016/j.chembiol.2014.02.021. Epub 2014 Apr 10. PMID: 24726831 Free Article</br>8:VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1. Ren HY, Grove DE, De La Rosa O, Houck SA, Sopha P, Van Goor F, Hoffman BJ, Cyr DM.Mol Biol Cell. 2013 Oct;24(19):3016-24. doi: 10.1091/mbc.E13-05-0240. Epub 2013 Aug 7. PMID: 23924900 Free PMC Article</br>9:Revertants, low temperature, and correctors reveal the mechanism of F508del-CFTR rescue by VX-809 and suggest multiple agents for full correction. Farinha CM, King-Underwood J, Sousa M, Correia AR, Henriques BJ, Roxo-Rosa M, Da Paula AC, Williams J, Hirst S, Gomes CM, Amaral MD.Chem Biol. 2013 Jul 25;20(7):943-55. doi: 10.1016/j.chembiol.2013.06.004. PMID: 23890012 Free Article</br>10:Corrector VX-809 stabilizes the first transmembrane domain of CFTR. Loo TW, Bartlett MC, Clarke DM.Biochem Pharmacol. 2013 Sep 1;86(5):612-9. doi: 10.1016/j.bcp.2013.06.028. Epub 2013 Jul 5. PMID: 23835419 |
