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Review
. 2022 Dec 16:13:1072651.
doi: 10.3389/fphar.2022.1072651. eCollection 2022.

Recent progress in DNA methyltransferase inhibitors as anticancer agents

Zhixiong Zhang  1   2 , Guan Wang  1 , Yuyan Li  1   2 , Dongsheng Lei  3 , Jin Xiang  1 , Liang Ouyang  1   4 , Yanyan Wang  1   4 , Jinliang Yang  1
Affiliations
Review

Recent progress in DNA methyltransferase inhibitors as anticancer agents

Zhixiong Zhang et al. Front Pharmacol. .

Abstract

DNA methylation mediated by DNA methyltransferase is an important epigenetic process that regulates gene expression in mammals, which plays a key role in silencing certain genes, such as tumor suppressor genes, in cancer, and it has become a promising therapeutic target for cancer treatment. Similar to other epigenetic targets, DNA methyltransferase can also be modulated by chemical agents. Four agents have already been approved to treat hematological cancers. In order to promote the development of a DNA methyltransferase inhibitor as an anti-tumor agent, in the current review, we discuss the relationship between DNA methylation and tumor, the anti-tumor mechanism, the research progress and pharmacological properties of DNA methyltransferase inhibitors, and the future research trend of DNA methyltransferase inhibitors.

Keywords: DNA methylation; DNA methyltransferase; DNA methyltransferase inhibitor; epigenetic; tumor immunotherapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Process and mechanism of DNA methylation. (A) The overall process of CpG methylation by DNMT. (B) Mechanism of DNA methylation in DNA (cytosine-5)-methyltransferase. (C) Crystal structure of human DNA methyltransferase 1 with AdoHcy (PBD code: 4WXX). The RFTS, CXXC, MTase, and BAH domains are colored in green, black, light blue, and yellow, respectively. SAH is colored in pink and residue C1226 is colored in gray.
FIGURE 2
FIGURE 2
Regulation of DNMTis on immune cells.
FIGURE 3
FIGURE 3
Chemical structure of DNMTis approved by the FDA.
FIGURE 4
FIGURE 4
Chemical structure of DNMTis in clinical.
FIGURE 5
FIGURE 5
Chemical structure of nucleoside DNMTis in preclinical.
FIGURE 6
FIGURE 6
Chemical structure of indole-based DNMTis in preclinical.
FIGURE 7
FIGURE 7
Chemical structure of carbazole-based DNMTis in pre-clinical.
FIGURE 8
FIGURE 8
Chemical structure of quinolone- and quinazoline-based DNMTis in pre-clinical.
FIGURE 9
FIGURE 9
Chemical structure of bromotyrosine-based DNMTis in pre-clinical.
FIGURE 10
FIGURE 10
Chemical structure of other DNMTis in pre-clinical.
See this image and copyright information in PMC

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Grants and funding

This work was supported by grants from the Technological Special Project for “Significant New Drugs Development” (Grant Nos. 2018ZX09201018-021 and 2018ZX09201018-020), the National Natural Science Foundation of China (Grant No. 82073318), the National Major Scientific and Sichuan Science and Technology Program (Grant No. 2019YFS0003), the National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Grant No. Z20201004), the Post-Doctor Research Project, West China Hospital, Sichuan University (2020HXBH020), the Science and Technology Project of the Health Planning Committee of Sichuan (20PJ022), and the Ministry of Science and Technology Project of the People’s Republic of China (2018YFC2001802-1).

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