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Updated: May 21, 2025

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
Published on: January 12, 2024
Application of mass spectrometry for the advancement of PROTACs
Yuechen Hao1, Baoshuang Zhang1, Ruibing Chen1
1School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China.
Abstract:
The advent of targeted protein degradation technologies, particularly Proteolysis-Targeting Chimeras (PROTACs), enable the selective elimination of target proteins and open up new avenues for the treatment of various diseases. This review delves into the pivotal role of mass spectrometry (MS) in the advancement of PROTACs. MS-based methodologies serve as invaluable tools for identifying PROTAC targets, validating their efficacy, and elucidating ubiquitination sites and protein degradation dynamics. These insights profoundly enrich our comprehension of the mechanisms of action and facilitate the rational design of PROTACs. Furthermore, this review discusses the role of MS in the structural analysis of proteins and the formation of ternary complexes crucial for the activity of PROTACs. The synergy between MS and PROTAC technology holds the promise of groundbreaking advancements in drug discovery by deepening our understanding of the underlying mechanisms that govern PROTAC drug action, thereby promoting the development of innovative strategies for disease treatment.
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