Computer-Assisted Discovery and Structural Optimization of a Novel Retinoid X Receptor Agonist Chemotype.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
14 Feb 2019
14 Feb 2019
Historique:
received:
16
11
2018
accepted:
27
12
2018
entrez:
21
2
2019
pubmed:
21
2
2019
medline:
21
2
2019
Statut:
epublish
Résumé
As universal heterodimer partners of many nuclear receptors, the retinoid X receptors (RXRs) constitute key transcription factors. They regulate cell proliferation, differentiation, inflammation, and metabolic homeostasis and have recently been proposed as potential drug targets for neurodegenerative and inflammatory diseases. Owing to the hydrophobic nature of RXR ligand binding sites, available synthetic RXR ligands are lipophilic, and their structural diversity is limited. Here, we disclose the computer-assisted discovery of a novel RXR agonist chemotype and its systematic optimization toward potent RXR modulators. We have developed a nanomolar RXR agonist with high selectivity among nuclear receptors and superior physicochemical properties compared to classical rexinoids that appears suitable for
Identifiants
pubmed: 30783504
doi: 10.1021/acsmedchemlett.8b00551
pmc: PMC6378677
doi:
Types de publication
Journal Article
Langues
eng
Pagination
203-208Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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