The development of small molecules targeting methyltransferase-like 3

Hongyu Li; Qiong Zhang; Qinglan Feng; Qidong You; Xiaoke Guo

doi:10.1016/j.drudis.2023.103513

The development of small molecules targeting methyltransferase-like 3

Drug Discov Today. 2023 Apr;28(4):103513. doi: 10.1016/j.drudis.2023.103513. Epub 2023 Feb 2.

Authors

Hongyu Li¹, Qiong Zhang², Qinglan Feng³, Qidong You⁴, Xiaoke Guo⁵

Affiliations

¹ Jiang Su Key Laboratory of Drug Design and Optimization and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 3220010071@stu.cpu.edu.cn.
² Jiang Su Key Laboratory of Drug Design and Optimization and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpu_zhangqiong@126.com.
³ Jiang Su Key Laboratory of Drug Design and Optimization and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 3220010088@stu.cpu.edu.cn.
⁴ Jiang Su Key Laboratory of Drug Design and Optimization and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: youqd@163.com.
⁵ Jiang Su Key Laboratory of Drug Design and Optimization and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: kexin95@126.com.

PMID: 36736582
DOI: 10.1016/j.drudis.2023.103513

Abstract

In mammals, N⁶-methyladenosine (m⁶A) is thought to be the most common and conserved mRNA modification. Methyltransferase-like 3 (METTL3) is the primary regulator of m⁶A methyl-transformed modification. Small molecules targeting METTL3 could be effective therapeutics for many disorders, given that a large body of research has linked METTL3 dysregulation with a variety of diseases and altered physiological states, especially with the growth and initiation of cancer. Here, we systematically reviewed the discovery of small molecules targeting METTL3, as well as their future development, for researchers studying in the field.

Keywords: METTL3; drug discovery; epigenetic; m(6)A; small molecule.

Publication types

Systematic Review
Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Mammals*
Methyltransferases*

Substances

Methyltransferases