Small-molecule inhibitors of the PDZ domain of Dishevelled proteins interrupt Wnt signalling.
Journal
Magnetic resonance (Gottingen, Germany)
ISSN: 2699-0016
Titre abrégé: Magn Reson (Gott)
Pays: Germany
ID NLM: 101775538
Informations de publication
Date de publication:
2021
2021
Historique:
received:
17
02
2021
accepted:
28
04
2021
medline:
2
6
2021
pubmed:
2
6
2021
entrez:
31
10
2023
Statut:
epublish
Résumé
Dishevelled (Dvl) proteins are important regulators of the Wnt signalling pathway, interacting through their PDZ domains with the Wnt receptor Frizzled. Blocking the Dvl PDZ-Frizzled interaction represents a potential approach for cancer treatment, which stimulated the identification of small-molecule inhibitors, among them the anti-inflammatory drug Sulindac and Ky-02327. Aiming to develop tighter binding compounds without side effects, we investigated structure-activity relationships of sulfonamides. X-ray crystallography showed high complementarity of anthranilic acid derivatives in the GLGF loop cavity and space for ligand growth towards the PDZ surface. Our best binding compound inhibits Wnt signalling in a dose-dependent manner as demonstrated by TOP-GFP assays (IC
Identifiants
pubmed: 37904770
doi: 10.5194/mr-2-355-2021
pii: 01021829
pmc: PMC10539800
doi:
Types de publication
Journal Article
Langues
eng
Pagination
355-374Informations de copyright
Copyright: © 2021 Nestor Kamdem et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflict of interest.
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