Targeting the ubiquitin system by fragment-based drug discovery.
chemical tools
drug discovery
fragment-based drug discovery
ubiquitin
ubiquitination
Journal
Frontiers in molecular biosciences
ISSN: 2296-889X
Titre abrégé: Front Mol Biosci
Pays: Switzerland
ID NLM: 101653173
Informations de publication
Date de publication:
2022
2022
Historique:
received:
15
08
2022
accepted:
05
09
2022
entrez:
24
10
2022
pubmed:
25
10
2022
medline:
25
10
2022
Statut:
epublish
Résumé
The ubiquitin system contains a wealth of potential drug targets for many diseases and conditions, including neurodegenerative, immune, metabolic and developmental diseases, as well as multiple cancers. Despite years of research, relatively few clinical inhibitors or specific chemical probes for proteins within the ubiquitin system exist, with many interesting target proteins yet to be explored. Fragment-based drug discovery (FBDD) offers efficient and broad coverage of chemical space with small libraries, using covalent and non-covalent approaches. Coupled with advances in structural biology and proteomics, FBDD now provides a thorough screening platform for inhibitor discovery within the ubiquitin system. In this mini review, we summarise the current scope of FBDD and how it has been applied to ubiquitin-activating (E1), ubiquitin-conjugating (E2), ubiquitin ligase (E3) and deubiquitinating (DUB) enzymes. We also discuss the newest frontiers of FBDD and how they could be applied to enable inhibitor and novel chemical probe discovery and provide functional insight into the ubiquitin system.
Identifiants
pubmed: 36275626
doi: 10.3389/fmolb.2022.1019636
pii: 1019636
pmc: PMC9580268
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1019636Informations de copyright
Copyright © 2022 Kennedy, McPhie and Rittinger.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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