Discovery of a Dual SENP1 and SENP2 Inhibitor.
SENP
cancer
deubiquitinating enzymes
drug discovery
inhibitors
medicinal chemistry
small molecules
structure activity relationship
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:
11 Oct 2022
11 Oct 2022
Historique:
received:
10
09
2022
revised:
24
09
2022
accepted:
05
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
29
10
2022
Statut:
epublish
Résumé
SUMOylation is a reversible post-translational modification (PTM) involving covalent attachment of small ubiquitin-related modifier (SUMO) proteins to substrate proteins. Dysregulation of SUMOylation and deSUMOylation results in cellular malfunction and is linked to various diseases, such as cancer. Sentrin-specific proteases (SENPs) were identified for the maturation of SUMOs and the deconjugation of SUMOs from their substrate proteins. Hence, this is a promising target tackling the dysregulation of the SUMOylation process. Herein, we report the discovery of a novel protein-protein interaction (PPI) inhibitor for SENP1-SUMO1 by virtual screening and subsequent medicinal chemistry optimization of the hit molecule. The optimized inhibitor ZHAWOC8697 showed IC
Identifiants
pubmed: 36292935
pii: ijms232012085
doi: 10.3390/ijms232012085
pmc: PMC9602571
pii:
doi:
Substances chimiques
sulfoenolpyruvate
118319-52-1
Small Ubiquitin-Related Modifier Proteins
0
Pyruvates
0
Endopeptidases
EC 3.4.-
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Zurich University of Applied Sciences
ID : AS 2021
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