Targeting USP-7 by a Novel Fluorinated 5-Pyrazolyl-Urea Derivative.
DARTS
USP-7
molecular docking
neuroblastoma
pyrazole derivative
t-LIP-MRM
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:
24 May 2023
24 May 2023
Historique:
received:
04
05
2023
revised:
17
05
2023
accepted:
23
05
2023
medline:
12
6
2023
pubmed:
10
6
2023
entrez:
10
6
2023
Statut:
epublish
Résumé
The impact of innovative technologies on the target discovery has been employed here to characterize the interactome of STIRUR 41, a promising 3-fluoro-phenyl-5-pyrazolyl-urea derivative endowed with anti-cancer activity, on neuroblastoma-related cells. A drug affinity responsive target stability-based proteomic platform has been optimized to elucidate the molecular mechanism at the basis of STIRUR 41 action, together with immunoblotting analysis and in silico molecular docking. Ubiquitin Specific Protease 7 (USP-7), one of the deubiquitinating enzymes which protect substrate proteins from proteasomal degradation, has been identified as the most affine STIRUR 41 target. As further demonstrated by in vitro and in-cell assays, STIRUR 41 was able to inhibit both the enzymatic activity of USP-7 and its expression levels in neuroblastoma-related cells, thus laying an encouraging base for the blockade of USP-7 downstream signaling.
Identifiants
pubmed: 37298148
pii: ijms24119200
doi: 10.3390/ijms24119200
pmc: PMC10252683
pii:
doi:
Substances chimiques
Urea
8W8T17847W
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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