Epigenetics-targeted drugs:current paradigms and future challenges

扫码查看

原文链接

万方数据

外文摘要：Epigenetics governs a chromatin state regulatory system through five key mechanisms:DNA modification,histone modification,RNA modification,chromatin remodeling,and non-coding RNA regulation.These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences,playing essential roles in organismal development and homeostasis.Conversely,disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases.This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifying enzymes in pathological conditions.Over the past two decades,a growing array of small molecule drugs targeting epigenetic enzymes such as DNA methyltransferase,histone deacetylase,isocitrate dehydrogenase,and enhancer of zeste homolog 2,have been thoroughly investigated and implemented as therapeutic options,particularly in oncology.Additionally,numerous epigenetics-targeted drugs are undergoing clinical trials,offering promising prospects for clinical benefits.This review delineates the roles of epigenetics in physiological and pathological contexts and underscores pioneering studies on the discovery and clinical implementation of epigenetics-targeted drugs.These include inhibitors,agonists,degraders,and multitarget agents,aiming to identify practical challenges and promising avenues for future research.Ultimately,this review aims to deepen the understanding of epigenetics-oriented therapeutic strategies and their further application in clinical settings.

作者：

Wanlin Dai、Xinbo Qiao、Yuanyuan Fang、Renhao Guo、Peng Bai、Shuang Liu、Tingting Li、Yutao Jiang、Shuang Wei、Zhijing Na、Xue Xiao、Da Li

展开 >

作者单位：

Center of Reproductive Medicine,Department of Obstetrics and Gynecology,Shengjing Hospital of China Medical University,Shenyang,China

Department of Orthopedics,Shengjing Hospital of China Medical University,Shenyang,China

Department of Forensic Genetics,West China School of Basic Medical Sciences & Forensic Medicine,Sichuan University,Chengdu,China

Shenyang Maternity and Child Health Hospital,Shenyang,China

Department of General Internal Medicine VIP Ward,Liaoning Cancer Hospital &Institute,Shenyang,China

NHC Key Laboratory of Advanced Reproductive Medicine and Fertility(China Medical University),National Health Commission,Shenyang,China

Department of Gynecology and Obstetrics,West China Second Hospital,Sichuan University,Chengdu,China

Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University),Ministry of Education,West China Second Hospital,Sichuan University,Chengdu,China

Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province,Shenyang,China

展开 >

出版年：

2024

DOI：

10.1038/S41392-024-02039-0

信号转导与靶向治疗(英文)

CSTPCD

ISSN：

年,卷(期)：2024.9(12)