Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1
Résumé
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Background: Finerenone is a novel nonsteroidal mineralocorticoid antagonist, currently in clinical phase IIb trials. Results: Finerenone delays mineralocorticoid receptor nuclear import and inhibits its binding and transcriptional coactivator recruitment onto target gene promoters. Conclusion: Finerenone impedes three critical steps of the mineralocorticoid receptor signaling pathway. Significance: Finerenone, which behaves differently from currently available mineralocorticoid antagonists, is potentially a promising molecule to treat cardiorenal diseases.
Mots clés
kinetics
rat
humans
hypertension
dose-response relationship
drug
transcriptional activation
mutation
signal transduction
chromatin immunoprecipitation
aldosterone
target genes
cell line
kidney
cell nucleus
protein binding
critical steps
binding
active transport
blotting
western
hek293 cells
promoter regions
genetic
down-regulation
microscopy
fluorescence
nuclear import
steroid receptor coactivator-1
mineralocorticoid receptors
transcriptional co-activators
epithelial sodium channels
naphthyridines
nuclear receptor coactivator 1
receptors
mineralocorticoid
spironolactone
antagonists
living cells
heart-failure
estrogen-receptor
bay 94-8862
spirolactones
Domaines
ChimieOrigine | Fichiers éditeurs autorisés sur une archive ouverte |
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