Proteolysis Targeting Chimeras (PROTACs): A Perspective on Integral Membrane Protein Degradation
Citations Over TimeTop 10% of 2022 papers
Abstract
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.
Related Papers
- → The membrane proteome of Halobacterium salinarum(2005)102 cited
- → Proteomic analysis of low-abundant integral plasma membrane proteins based on gels(2006)43 cited
- → Identification and bioinformatic analysis of the membrane proteins of synechocystis sp. PCC 6803(2009)24 cited
- → Large-scale identification of membrane proteins based on analysis of trypsin-protected transmembrane segments(2016)17 cited
- → A three-pronged “Pitchfork” strategy enables an extensive description of the human membrane proteome and the identification of missing proteins(2019)8 cited