A high throughput screen for pharmacological inhibitors of the carbohydrate response element.
Journal
Scientific data
ISSN: 2052-4463
Titre abrégé: Sci Data
Pays: England
ID NLM: 101640192
Informations de publication
Date de publication:
04 10 2023
04 10 2023
Historique:
received:
04
04
2023
accepted:
26
09
2023
medline:
2
11
2023
pubmed:
5
10
2023
entrez:
4
10
2023
Statut:
epublish
Résumé
A central regulator of metabolism, transcription factor carbohydrate response element binding protein (ChREBP) senses and responds to dietary glucose levels by stimulating the transcription of glycolytic and lipogenic enzymes. Genetic depletion of ChREBP rescues β-cell dysfunction arising from high glucose levels, suggesting that inhibiting ChREBP might represent an attractive therapeutic approach to manage diabetes and other metabolic diseases. However, the molecular mechanisms governing ChREBP activation are poorly understood and chemical tools to probe the cellular activity of ChREBP are lacking. Here, we report a high-throughput pharmacological screen in INS-1E β-cells that identified novel inhibitors of ChREBP-driven transcription at carbohydrate response element sites, including three putative covalent inhibitors and two likely non-covalent chemical scaffolds. This work affords a pharmacological toolkit to help uncover the signaling logic controlling ChREBP activation and may ultimately reveal potential therapeutic approaches for treating metabolic disease.
Identifiants
pubmed: 37794069
doi: 10.1038/s41597-023-02596-z
pii: 10.1038/s41597-023-02596-z
pmc: PMC10550954
doi:
Substances chimiques
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
0
Glucose
IY9XDZ35W2
Transcription Factors
0
Types de publication
Dataset
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
676Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM146865
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
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