Low Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR.
RNA pulldown assay
RNA-binding protein
high-throughput virtual screening
human antigen R (HuR)
small molecule inhibitors
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
23 Aug 2023
23 Aug 2023
Historique:
received:
31
07
2023
revised:
18
08
2023
accepted:
22
08
2023
medline:
11
9
2023
pubmed:
9
9
2023
entrez:
9
9
2023
Statut:
epublish
Résumé
The RNA-binding protein human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. This protein has been progressively recognized as a relevant therapeutic target for several pathologies, like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here, we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatic approaches, high-throughput virtual screening, and RNA-protein pulldown assays, we demonstrate that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits a dose-dependent HuR inhibition effect in binding experiments. Importantly, the chemical scaffold is new with respect to the currently known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.
Identifiants
pubmed: 37685931
pii: ijms241713127
doi: 10.3390/ijms241713127
pmc: PMC10488267
pii:
doi:
Substances chimiques
Benzoates
0
RNA-Binding Proteins
0
ELAV-Like Protein 1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : German Federal Ministry of Education and Research (BMBF)
ID : 01DP19004
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