Proteolysis Targeting Chimeras (PROTACs): A Perspective on Integral Membrane Protein Degradation.
Journal
ACS pharmacology & translational science
ISSN: 2575-9108
Titre abrégé: ACS Pharmacol Transl Sci
Pays: United States
ID NLM: 101721411
Informations de publication
Date de publication:
14 Oct 2022
14 Oct 2022
Historique:
received:
22
07
2022
entrez:
21
10
2022
pubmed:
22
10
2022
medline:
22
10
2022
Statut:
epublish
Résumé
Targeted protein degradation (TPD) is a promising therapeutic modality to modulate protein levels and its application promises to reduce the "undruggable" proteome. Among TPD strategies, Proteolysis TArgeting Chimera (PROTAC) technology has shown a tremendous potential with attractive advantages when compared to the inhibition of the same target. While PROTAC technology has had a significant impact in scientific research, its application to degrade integral membrane proteins (IMPs) is still in its beginnings. Among the 15 compounds having entered clinical trials by the end of 2021, only two targets are membrane-associated proteins. In this review we are discussing the potential reasons which may underlie this, and we are presenting new tools that have been recently developed to solve these limitations and to empower the use of PROTACs to target IMPs.
Identifiants
pubmed: 36268122
doi: 10.1021/acsptsci.2c00142
pmc: PMC9578132
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
849-858Informations de copyright
© 2022 The Authors. Published by American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare the following competing financial interest(s): Camilla Ruffilli, Sascha Roth, Monica Rodrigo, Helen Boyd, and Kevin Moreau are all AstraZeneca employees.
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