Review Article

Proteomic characterization of post-translational modifications in drug discovery

Lin-hui Zhai1,2,3, Kai-feng Chen1,2, Bing-bing Hao1, Min-jia Tan1,2,3
1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2 University of Chinese Academy of Sciences, Beijing 100049, China
3 Zhongshan Institute of Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Science, Zhongshan 528400, China
Correspondence to: Min-jia Tan:,
DOI: 10.1038/s41401-022-01017-y
Received: 10 June 2022
Accepted: 7 August 2022
Advance online: 13 November 2022


Protein post-translational modifications (PTMs), which are usually enzymatically catalyzed, are major regulators of protein activity and involved in almost all celluar processes. Dysregulation of PTMs is associated with various types of diseases. Therefore, PTM regulatory enzymes represent as an attractive and important class of targets in drug research and development. Inhibitors against kinases, methyltransferases, deacetyltransferases, ubiquitin ligases have achieved remarkable success in clinical application. Mass spectrometry-based proteomics technologies serve as a powerful approach for system-wide characterization of PTMs, which facilitates the identification of drug targets, elucidation of the mechanisms of action of drugs, and discovery of biomakers in personalized therapy. In this review, we summarize recent advances of proteomics-based studies on PTM targeting drugs and discuss how proteomics strategies facilicate drug target identification, mechanism elucidation, and new therapy development in precision medicine.
Keywords: proteomics; protein post-translational modification; drug target; off-target; drug mechanism; precision medicine

Article Options

Download Citation

Cited times in Scopus