ABCMdb

PMID: 24726831

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
VX-809 and related corrector compounds exhibit secondary activity stabilizing active F508del-CFTR after its partial rescue to the cell surface.
Chem Biol. 2014 May 22;21(5):666-78. doi: 10.1016/j.chembiol.2014.02.021. Epub 2014 Apr 10., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Gly551Asp INTRODUCTION The field of cystic fibrosis (CF) research has been galvanized by the discovery of a new compound called VX-770 or KALYDECO (ivacaftor; Vertex Pharmaceuticals), a compound described as a ''potentiator`` because it repairs the defective channel function caused by the mutation G551D, a relatively rare mutation found in <4% of the CF patient population (Accurso et al., 2010; Van Goor et al., 2009). Login to comment 25 ABCC7 p.Arg1070Trp To date, however, there have been conflicting reports regarding the consequences of mutations at the NBD1-ICL4 interface (including R1070W) on the efficacy of VX-809 in in-cell maturation studies (He et al., 2013; Okiyoneda et al., 2013), prompting speculation that VX-809 may not bind directly to this site on the mutant protein. Login to comment 231 ABCC7 p.Glu60* This ''priming`` or potentiating effect was not observed in intestinal organoids generated from a patient bearing a CFTR nonsense mutation (E60X/4015 delATT, inset) showing that it is mediated by rescued F508del-CFTR rather than a non-CFTR channel. Login to comment