Targeting different binding sites in the CFTR structures allows to synergistically potentiate channel activity.
3D structure
CFTR
Combinatorial therapies
Halide-sensitive fluorescence
Modulator
Ussing chamber
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Mar 2020
15 Mar 2020
Historique:
received:
16
08
2019
revised:
24
01
2020
accepted:
03
02
2020
pubmed:
23
2
2020
medline:
15
12
2020
entrez:
21
2
2020
Statut:
ppublish
Résumé
Recent evidence shows that combination of correctors and potentiators, such as the drug ivacaftor (VX-770), can significantly restore the functional expression of mutated Cystic Fibrosis Transmembrane conductance Regulator (CFTR), an anion channel which is mutated in cystic fibrosis (CF). The success of these combinatorial therapies highlights the necessity of identifying a broad panel of specific binding mode modulators, occupying several distinct binding sites at structural level. Here, we identified two small molecules, SBC040 and SBC219, which are two efficient cAMP-independent potentiators, acting at low concentration of forskolin with EC
Identifiants
pubmed: 32078860
pii: S0223-5234(20)30083-0
doi: 10.1016/j.ejmech.2020.112116
pii:
doi:
Substances chimiques
Aminophenols
0
Benzamides
0
CFTR protein, human
0
Purines
0
Quinolones
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
ivacaftor
1Y740ILL1Z
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112116Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following competing financial interest related to their patent: Compounds for treating cystic fibrosis. I. Callebaut, J.-P. Mornon J.-L. Décout, F. Becq, Pierre Lehn, Brice Hoffmann, B. Boucherle, A. Fortuné, R. Haudecoeur, C. Boinot, WO 2016 087665 A2 20160609.