Application of mass spectrometry for the advancement of PROTACs

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2025-03-19 DOI:10.1016/j.jpba.2025.116829

Yuechen Hao, Baoshuang Zhang, Ruibing Chen

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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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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.