Approved drugs ezetimibe and disulfiram enhance mitochondrial Ca
Animals
Arrhythmias, Cardiac
/ chemically induced
Calcium
/ metabolism
Calcium Signaling
Disulfiram
/ metabolism
Ezetimibe
/ metabolism
HeLa Cells
Humans
Mice
Mitochondria
/ metabolism
Myocytes, Cardiac
/ metabolism
Pharmaceutical Preparations
/ metabolism
Ryanodine Receptor Calcium Release Channel
/ metabolism
Tachycardia, Ventricular
/ metabolism
Zebrafish
/ metabolism
CPVT
MCU
anti-arrhythmic
arrhythmia
mitochondria
mitochondrial Ca2+ uptake enhancers
mitochondrial Ca2+ uptake pathway
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
21
06
2021
received:
26
11
2020
accepted:
30
06
2021
pubmed:
22
7
2021
medline:
15
12
2021
entrez:
21
7
2021
Statut:
ppublish
Résumé
Treatment of cardiac arrhythmia remains challenging due to severe side effects of common anti-arrhythmic drugs. We previously demonstrated that mitochondrial Ca Herewe screened 727 compounds with a history of use in human clinical trials in a three-step screening approach. As a primary screening platform we used a permeabilized HeLa cell-based mitochondrial Ca We identifiedtwo candidate compounds, the clinically approved drugs ezetimibe and disulfiram, which stimulate SR-mitochondria Ca Taken together we identified ezetimibe and disulfiram as novel MiCUps and efficient suppressors of arrhythmogenesis and as such as, promising candidates for future preclinical and clinical studies.
Sections du résumé
BACKGROUND AND PURPOSE
Treatment of cardiac arrhythmia remains challenging due to severe side effects of common anti-arrhythmic drugs. We previously demonstrated that mitochondrial Ca
EXPERIMENTAL APPROACH
Herewe screened 727 compounds with a history of use in human clinical trials in a three-step screening approach. As a primary screening platform we used a permeabilized HeLa cell-based mitochondrial Ca
KEY RESULTS
We identifiedtwo candidate compounds, the clinically approved drugs ezetimibe and disulfiram, which stimulate SR-mitochondria Ca
CONCLUSION AND IMPLICATIONS
Taken together we identified ezetimibe and disulfiram as novel MiCUps and efficient suppressors of arrhythmogenesis and as such as, promising candidates for future preclinical and clinical studies.
Substances chimiques
Pharmaceutical Preparations
0
Ryanodine Receptor Calcium Release Channel
0
Ezetimibe
EOR26LQQ24
Calcium
SY7Q814VUP
Disulfiram
TR3MLJ1UAI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4518-4532Informations de copyright
© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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