Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies

查看全文 作　　者：Xiaopeng [1]Peng;Zhihao [1]Hu;Limei [2]Zeng;Meizhu [1]Zhang;Congcong [1]Xu;Benyan [1]Lu;Chengpeng [1]Tao;Weiming [1]Chen;Wen [1]Hou;Kui [3]Cheng;Huichang [3]Bi;Wanyi [1]Pan;Jianjun [3]Chen

机构地区：[1]College of Pharmacy,Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education,Gannan Medical University,Ganzhou 314000,China;[2]College of Basic Medicine,Gannan Medical University,Ganzhou 314000,China;[3]Guangdong Provincial Key Laboratory of New Drug Screening,NMPA Key Laboratory for Research and Evaluation of Drug Metabolism,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China

出　　处：《Acta Pharmaceutica Sinica B》索引2024年第14卷第2期,共46页

基　　金：supported by the National Natural Science Foundation of China(Nos.82173668,82260676);Jiangxi Provincial Natural Science Foundation(20232BAB216131,China);the Scientific and Technological Key Projects of Guangdong Province(Nos.2021B1111110003,2019B020202002,China);the Science and Technology Projects of Ganzhou(202101094462,China);the Start-Up Foundation of Gannan Medical University(No.QD202144-2067,China). 摘　　要：Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges,including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result,the design of new epigenetic modulators(e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging(Hy T) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review,we aim to provide an in-depth illustration of new degrading strategies(2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders. 关键词：EPIGENETIC Degrader PROTAC Molecularglue Hydrophobic tagging

相关文献

参考文献（188）
引证文献（3）
耦合文献（364）

参考文献(188)

引证文献(3)

耦合文献(364)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies

参考文献(188)

引证文献(3)

耦合文献(364)

用户提示