ABCMdb

PMID: 21108631

Cuthbert AW
New horizons in the treatment of cystic fibrosis.
Br J Pharmacol. 2011 May;163(1):173-83. doi: 10.1111/j.1476-5381.2010.01137.x., [PubMed]

Sentences

No. Mutations Sentence Comment

164 ABCC7 p.Gly551Asp Class 3 mutations produce CFTR in which the regulation of the ion channel is disturbed, as in G551D, a relatively common mutation accounting for 3% of CF mutations. Login to comment 165 ABCC7 p.Arg117His Class 4 mutations allow the CFTR protein to be correctly translocated to the cell membrane but with reduced ion fluxes and altered selectivity because of mutations affecting the pore region of the channel, as in R117H. Login to comment 181 ABCC7 p.Gly551Asp Epithelial cells (usually Fischer rat thyroid cells) expressing DF508 CFTR (or CFTR or G551D CFTR) together with the yellow fluorescent protein YP-H148Q that fluoresces in the presence of Cl- ions but not with I- ions, are grown on 100-well plates. Login to comment 193 ABCC7 p.Gly551Asp Screening of a small library of benzoquinolizinium compounds showed that some of these not only activated CFTR, DF508 CFTR and G551D but also redirected the mutant forms to the correct cell location; that is, they were both correctors and potentiators (Becq et al., 1999; Dormer et al., 2001). Login to comment 211 ABCC7 p.Gly551Asp For example, many of the antihypertensive 1,4 dihydropyridines, like nifedipine, nicardipine and nimodipine activated CFTR, DF508 CFTR and G551D (Pedemonte et al., 2005a). Login to comment 225 ABCC7 p.Gly551Asp ABCC7 p.Arg117His VX-770 was chosen on its ability to potentiate several forms of CFTR, including CFTR, G551D and R117H. Login to comment 228 ABCC7 p.Gly551Asp In HBE cultures carrying both the G551D and the DF508 mutations VX-770 increased chloride secretion by ~10-fold, to ~50% of that observed in wild-type HBE epithelia. Login to comment 230 ABCC7 p.Gly551Asp The initial clinical trial with VX770 was for patients with G551D mutations (~3% of the CF population) as the mutant protein is delivered to the membrane but cannot be activated. Login to comment 231 ABCC7 p.Gly551Asp Patch clamping studies showed that when expressed in FRT cells, the Po of G551D was increased from 0.1 to 0.45 by VX-770, while with DF508 CFTR, Po increased from 0.08 to 0.52 (Van Goor et al., 2009). Login to comment 251 ABCC7 p.Arg258Gly ABCC7 p.Ser945Leu ABCC7 p.His949Tyr In one of these, VRT-325 rescued CFTR mutants R258G, S945L and H949Y as well as DF508 CFTR (Loo et al., 2005). Login to comment