ABCMdb

PMID: 16127463

Pedemonte N, Lukacs GL, Du K, Caci E, Zegarra-Moran O, Galietta LJ, Verkman AS
Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening.
J Clin Invest. 2005 Sep;115(9):2564-71. Epub 2005 Aug 25., [PubMed]

Sentences

No. Mutations Sentence Comment

9 ABCC7 p.Pro574His The bisaminomethylbithiazoles corrected ∆F508-CFTR in ∆F508/∆F508 human bronchial epithelia but did not correct a different temperature-sensitive CFTR mutant (P574H-CFTR) or a dopamine receptor mutant. Login to comment 115 ABCC7 p.Pro574His As an initial test of compound specificity for correction of defective ∆F508-CFTR processing, compounds were tested on P574H-CFTR, a mutant that like ∆F508-CFTR is retained at the ER but can be rescued by incubation for 24 hours at reduced temperature (26). Login to comment 119 ABCC7 p.Pro574His Figure 5A shows that corr-4a and -2a, which produced robust chloride currents in ∆F508-CFTR-expressing cells, did not produce significant correction in P574H-CFTR cells, despite a positive low-temperature rescue control. Login to comment 139 ABCC7 p.Asn1303Lys 2568 The Journal of Clinical Investigation http://www.jci.org Volume 115 Number 9 September 2005 subject homozygous for the N1303K-CFTR mutation, which also manifests defective CFTR processing (29). Login to comment 140 ABCC7 p.Asn1303Lys Figure 6C shows that there was no significant correction of short-circuit current for the N1303K-CFTR bronchial cells when measured with the same compounds and conditions used for the ∆F508-CFTR cells measured in Figure 6A. Login to comment 179 ABCC7 p.Pro574His (A) Apical membrane chloride current in FRT cells expressing the temperature-sensitive mutant P574H-CFTR. Login to comment 191 ABCC7 p.Asn1303Lys (C) Short-circuit current recordings of primary cultures of human bronchial epithelial cells from a homozygous N1303K-CFTR subject taken under conditions as described in A. Login to comment 193 ABCC7 p.Pro574His The lack of effect of some ∆F508-CFTR correctors on the temperature-sensitive mutant P574H-CFTR and the mutant DRD4-M345T suggests their specificity for the ∆F508 mutation, though further studies are needed to evaluate the numerous potential off-target specificities. Login to comment 202 ABCC7 p.Pro574His A similar approach was used to generate BHK cells coexpressing ∆F508-CFTR and YFP-H148Q/I152L and FRT cells stably expressing P574H-CFTR. Login to comment 209 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys Human nasal epithelial cells, which were obtained from ∆F508/∆F508 CF subjects (or an N1303K/N1303K subject) with informed consent, were cultured on Snapwell inserts and allowed to differentiate in a hormone-supplemented medium as described previously (36). Login to comment 328 ABCC7 p.Gly551Asp Pedemonte,N.,etal.2005.Phenylglycineandsulfon- amide correctors of defective ∆F508- and G551D-CFTR chloride channel gating. Login to comment 334 ABCC7 p.Gly551Asp Pedemonte,N.,etal.2005.Phenylglycineandsulfon- amide correctors of defective ∆F508- and G551D-CFTR chloride channel gating. Login to comment 358 ABCC7 p.Pro574His Processing of CFTR bearing the P574H mutation differs from wild-type and ∆F508-CFTR. Login to comment 365 ABCC7 p.Pro574His Processing of CFTR bearing the P574H mutation differs from wild-type and ∆F508-CFTR. Login to comment