Rational design and virtual screening identify mimetics of the RXR agonist valerenic acid.

natural product mimetic retinoid X receptor transcription factor

Journal

ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013

Informations de publication

Date de publication:
18 Jan 2024
Historique:
revised: 23 12 2023
received: 22 07 2023
accepted: 17 01 2024
medline: 18 1 2024
pubmed: 18 1 2024
entrez: 18 1 2024
Statut: aheadofprint

Résumé

The ligand-sensing transcription factor retinoid X receptor (RXR) is the universal heterodimer partner of nuclear receptors and involved in multiple physiological processes. Its pharmacological modulation holds therapeutic potential in cancer and neurodegeneration but many available RXR ligands lack specificity. The sesquiterpenoid valerenic acid has been identified as RXR agonist with unprecedented subtype and homodimer preference. Here, we identified simplified mimetics of the complex natural product by rational design and virtual screening that exhibited similar activity profiles on RXR and informed about structural elements contributing to the favorable activity.

Identifiants

pubmed: 38235922
doi: 10.1002/cmdc.202300379
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202300379

Informations de copyright

© 2024 Wiley-VCH GmbH.

Auteurs

Laura Isigkeit (L)

Goethe University Frankfurt: Goethe-Universitat Frankfurt am Main, Institute of Pharmaceutical Chemistry, GERMANY.

Annette Kärcher (A)

Goethe University Frankfurt: Goethe-Universitat Frankfurt am Main, Institute of Pharmaceutical Chemistry, GERMANY.

Gustave Adouvi (G)

Goethe University Frankfurt: Goethe-Universitat Frankfurt am Main, Institute of Pharnmaceutical Chemistry, GERMANY.

Silvia Arifi (S)

Goethe University Frankfurt: Goethe-Universitat Frankfurt am Main, Institute of Pharmaceutical Chemistry, GERMANY.

Daniel Merk (D)

Ludwig-Maximilians-Universität München: Ludwig-Maximilians-Universitat Munchen, Department of Pharmacy, Butenandtstr. 5-13, 91377, Munich, GERMANY.

Classifications MeSH