2. Academic Validation
  3. Overview of the development of protein arginine methyltransferase modulators: Achievements and future directions

Overview of the development of protein arginine methyltransferase modulators: Achievements and future directions

  • Eur J Med Chem. 2024 Mar 5:267:116212. doi: 10.1016/j.ejmech.2024.116212.
Chao Tong 1,  Xiujin Chang 1,  Fangui Qu 1,  Jinlei Bian 1,  Jubo Wang 2,  Zhiyu Li 3,  Xi Xu 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjin, 211198, China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjin, 211198, China. Electronic address: [email protected].
  • 3 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjin, 211198, China. Electronic address: [email protected].
  • 4 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjin, 211198, China. Electronic address: [email protected].
PMID: 38359536 DOI: 10.1016/j.ejmech.2024.116212
Abstract

Protein methylation is a post-translational modification (PTM) that organisms undergo. This process is considered a part of Epigenetics research. In recent years, there has been an increasing interest in protein methylation, particularly histone methylation, as research has advanced. Methylation of histones is a dynamic process that is subject to fine control by histone methyltransferases and demethylases. In addition, many non-histone proteins also undergo methylation, and these modifications collectively regulate physiological phenomena, including RNA transcription, translation, signal transduction, DNA damage response, and cell cycle. Protein arginine methylation is a crucial aspect of protein methylation, which plays a significant role in regulating the cell cycle and repairing DNA. It is also linked to various diseases. Therefore, protein arginine methyltransferases (PRMTs) that are involved in this process have gained considerable attention as a potential therapeutic target for treating diseases. Several PRMT inhibitors are in phase I/II clinical trials. This paper aims to introduce the structure, biochemical functions, and bioactivity assays of PRMTs. Additionally, we will review the structure-function of currently popular PRMT inhibitors. Through the analysis of various data on known PRMT inhibitors, we hope to provide valuable assistance for future drug design and development.

Keywords

Physiological effect; Post-translational modification; Protein arginine methyltransferase; Structure-activity relationships.

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