ABCMdb

PMID: 21275046

Noy E, Senderowitz H
Combating cystic fibrosis: in search for CF transmembrane conductance regulator (CFTR) modulators.
ChemMedChem. 2011 Feb 7;6(2):243-51. doi: 10.1002/cmdc.201000488. Epub 2011 Jan 14., 2011-02-07 [PubMed]

Sentences

No. Mutations Sentence Comment

14 ABCC7 p.Gly551Asp Another common mutation is glycine- to-aspartate at position 551 (G551D) in the signature motif of NBD1. Login to comment 19 ABCC7 p.Trp1282* ABCC7 p.Gly542* Class I mutations are found in ~10% of CF patients, and the most common ones are G542X and W1282X, the latter being particularly common in Ashkenazi Jews. Login to comment 38 ABCC7 p.Gly551Asp Vertex Pharmaceuticals developed VX-770, an orally bioavailable potentiator that is currently being evaluated in phase 3 clinical trials in patients carrying the G551D mutation and in patients homozygote for the DF508 mutation. Login to comment 71 ABCC7 p.Gly551Asp Secondary analysis and testing of over 1000 structural analogues yielded two novel classes of potentiators, phenylglycines and sulfonamides, with nanomolar potency that were active in human DF508 and G551D-CFTR expressing cells. Login to comment 93 ABCC7 p.Gly551Asp Springsteel et al.[41] used a series of 77 benzoflavone analogues to examine activation of G551D-CFTR and formulated a four-point pharmacophore featuring a hydrogen-bond acceptor, an aromatic ring and two hydrophobic groups. Login to comment 96 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp While P-ATP and dATP were found to potentiate the activity of G551D-CFTR by approximately sevenfold and eightfold, respectively, the chimeric ligand was found to potentiate G551D-CFTR by 36-fold, mainly by prolonging the open time of the channel. Login to comment