Druggability Evaluation of the Neuron Derived Orphan Receptor (NOR-1) Reveals Inverse NOR-1 Agonists.
NR4A3
fragment screening
neurodegeneration
nuclear receptor
transcription factor
Journal
ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013
Informations de publication
Date de publication:
17 08 2022
17 08 2022
Historique:
received:
09
05
2022
pubmed:
16
6
2022
medline:
20
8
2022
entrez:
15
6
2022
Statut:
ppublish
Résumé
The neuron derived orphan receptor (NOR-1, NR4A3) is among the least studied nuclear receptors. Its physiological role and therapeutic potential remain widely elusive which is in part due to the lack of chemical tools that can directly modulate NOR-1 activity. To probe the possibility of pharmacological NOR-1 modulation, we have tested a drug fragment library for NOR-1 activation and repression. Despite low hit-rate (<1 %), we have obtained three NOR-1 ligand chemotypes one of which could be rapidly expanded to an analogue comprising low micromolar inverse NOR-1 agonist potency and altering NOR-1 regulated gene expression in a cellular setting. It confirms druggability of the transcription factor and may serve as an early tool to assess the role and potential of NOR-1.
Identifiants
pubmed: 35704774
doi: 10.1002/cmdc.202200259
pmc: PMC9542104
doi:
Substances chimiques
Ligands
0
Receptors, Cytoplasmic and Nuclear
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202200259Informations de copyright
© 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH.
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