Uses
VX 809 is used in the stabilization of the CFTR protein used in the treatment of cystic fibrosis.
Definition
ChEBI: An aromatic amide obtained by formal condensation of the carboxy group of 1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropane-1-carboxylic acid with the aromatic amino group of 3-(6-amino-3-methylpyridin-2-yl)benzoic acid. Used for the treatment of cystic fi
rosis.
Biological Activity
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
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
