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Anion carriers as potential treatments for cystic fibrosis: transport in cystic fibrosis cells, and additivity to channel-targeting drugs

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Anion carriers as potential treatments for cystic fibrosis : transport in cystic fibrosis cells, and additivity to channel-targeting drugs. / Li, Hongyu; Valkenier, Hennie; Thorne, Abigail; Dias, Christopher M; Cooper, James A; Keiffer, Marion; Busschaert, Nathalie ; Gale, Philip A.; Sheppard, David N; Davis, Anthony P.

In: Chemical Science, Vol. 42, 02.10.2019, p. 9663-9672 .

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Li, H, Valkenier, H, Thorne, A, Dias, CM, Cooper, JA, Keiffer, M, Busschaert, N, Gale, PA, Sheppard, DN & Davis, AP 2019, 'Anion carriers as potential treatments for cystic fibrosis: transport in cystic fibrosis cells, and additivity to channel-targeting drugs', Chemical Science, vol. 42, pp. 9663-9672 . https://doi.org/10.1039/C9SC04242C

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Li, Hongyu ; Valkenier, Hennie ; Thorne, Abigail ; Dias, Christopher M ; Cooper, James A ; Keiffer, Marion ; Busschaert, Nathalie ; Gale, Philip A. ; Sheppard, David N ; Davis, Anthony P. / Anion carriers as potential treatments for cystic fibrosis : transport in cystic fibrosis cells, and additivity to channel-targeting drugs. In: Chemical Science. 2019 ; Vol. 42. pp. 9663-9672 .

Bibtex

@article{4061cbc70bd54693ba32ad5b4cb044c3,
title = "Anion carriers as potential treatments for cystic fibrosis: transport in cystic fibrosis cells, and additivity to channel-targeting drugs",
abstract = "Defective anion transport is a hallmark of the genetic disease cystic fibrosis (CF). One approach to restore anion transport to CF cells utilises alternative pathways for transmembrane anion transport, including artificial anion carriers (anionophores). Here, we screened 22 anionophores for biological activity using fluorescence emission from the halidesensitive yellow fluorescent protein. Three compounds possessed anion transport activity similar to or greater than that of a bis-(p-nitrophenyl)ureidodecalin previously shown to have promising biological activity. Anion transport by these anionophores was concentration-dependent and persistent. All four anionophores mediated anion transport in CF cells, and their activity was additive to rescue of the predominant disease-causing variant F508del-CFTR using the clinically licensed drugs lumacaftor and ivacaftor. Toxicity was variable but minimal at the lower end. The results provide further evidence that anionophores, by themselves or together with other treatments that restore anion transport, offer a potential therapeutic strategy for CF.",
author = "Hongyu Li and Hennie Valkenier and Abigail Thorne and Dias, {Christopher M} and Cooper, {James A} and Marion Keiffer and Nathalie Busschaert and Gale, {Philip A.} and Sheppard, {David N} and Davis, {Anthony P}",
year = "2019",
month = "10",
day = "2",
doi = "10.1039/C9SC04242C",
language = "English",
volume = "42",
pages = "9663--9672",
journal = "Chemical Science",
issn = "2041-6520",
publisher = "Royal Society of Chemistry",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Anion carriers as potential treatments for cystic fibrosis

T2 - transport in cystic fibrosis cells, and additivity to channel-targeting drugs

AU - Li, Hongyu

AU - Valkenier, Hennie

AU - Thorne, Abigail

AU - Dias, Christopher M

AU - Cooper, James A

AU - Keiffer, Marion

AU - Busschaert, Nathalie

AU - Gale, Philip A.

AU - Sheppard, David N

AU - Davis, Anthony P

PY - 2019/10/2

Y1 - 2019/10/2

N2 - Defective anion transport is a hallmark of the genetic disease cystic fibrosis (CF). One approach to restore anion transport to CF cells utilises alternative pathways for transmembrane anion transport, including artificial anion carriers (anionophores). Here, we screened 22 anionophores for biological activity using fluorescence emission from the halidesensitive yellow fluorescent protein. Three compounds possessed anion transport activity similar to or greater than that of a bis-(p-nitrophenyl)ureidodecalin previously shown to have promising biological activity. Anion transport by these anionophores was concentration-dependent and persistent. All four anionophores mediated anion transport in CF cells, and their activity was additive to rescue of the predominant disease-causing variant F508del-CFTR using the clinically licensed drugs lumacaftor and ivacaftor. Toxicity was variable but minimal at the lower end. The results provide further evidence that anionophores, by themselves or together with other treatments that restore anion transport, offer a potential therapeutic strategy for CF.

AB - Defective anion transport is a hallmark of the genetic disease cystic fibrosis (CF). One approach to restore anion transport to CF cells utilises alternative pathways for transmembrane anion transport, including artificial anion carriers (anionophores). Here, we screened 22 anionophores for biological activity using fluorescence emission from the halidesensitive yellow fluorescent protein. Three compounds possessed anion transport activity similar to or greater than that of a bis-(p-nitrophenyl)ureidodecalin previously shown to have promising biological activity. Anion transport by these anionophores was concentration-dependent and persistent. All four anionophores mediated anion transport in CF cells, and their activity was additive to rescue of the predominant disease-causing variant F508del-CFTR using the clinically licensed drugs lumacaftor and ivacaftor. Toxicity was variable but minimal at the lower end. The results provide further evidence that anionophores, by themselves or together with other treatments that restore anion transport, offer a potential therapeutic strategy for CF.

U2 - 10.1039/C9SC04242C

DO - 10.1039/C9SC04242C

M3 - Article

VL - 42

SP - 9663

EP - 9672

JO - Chemical Science

JF - Chemical Science

SN - 2041-6520

ER -