Recent advances in developing targeted protein degraders

IF 6 2区 医学 Q1 CHEMISTRY, MEDICINAL
Binbin Cheng , Hongqiao Li , Xiaopeng Peng , Jianjun Chen , Chuxiao Shao , Zhihua Kong
{"title":"Recent advances in developing targeted protein degraders","authors":"Binbin Cheng ,&nbsp;Hongqiao Li ,&nbsp;Xiaopeng Peng ,&nbsp;Jianjun Chen ,&nbsp;Chuxiao Shao ,&nbsp;Zhihua Kong","doi":"10.1016/j.ejmech.2024.117212","DOIUrl":null,"url":null,"abstract":"<div><div>Targeted protein degradation (TPD) represents a promising therapeutic approach, encompassing several innovative strategies, including but not limited to proteolysis targeting chimeras (PROTACs), molecular glues, hydrophobic tag tethering degraders (HyTTD), and lysosome-targeted chimeras (LYTACs). Central to TPD are small molecule ligands, which play a critical role in mediating the degradation of target proteins. This review summarizes the current landscape of small molecule ligands for TPD molecules. These small molecule ligands can utilize the proteasome, lysosome, autophagy, or hydrophobic-tagging system to achieve the degradation of target proteins. The article mainly focuses on introducing their design principles, application advantages, and potential limitations. A brief discussion on the development prospects and future directions of TPD technology was also provided.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"284 ","pages":"Article 117212"},"PeriodicalIF":6.0000,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0223523424010948","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Targeted protein degradation (TPD) represents a promising therapeutic approach, encompassing several innovative strategies, including but not limited to proteolysis targeting chimeras (PROTACs), molecular glues, hydrophobic tag tethering degraders (HyTTD), and lysosome-targeted chimeras (LYTACs). Central to TPD are small molecule ligands, which play a critical role in mediating the degradation of target proteins. This review summarizes the current landscape of small molecule ligands for TPD molecules. These small molecule ligands can utilize the proteasome, lysosome, autophagy, or hydrophobic-tagging system to achieve the degradation of target proteins. The article mainly focuses on introducing their design principles, application advantages, and potential limitations. A brief discussion on the development prospects and future directions of TPD technology was also provided.

Abstract Image

Abstract Image

靶向蛋白降解剂的研究进展
靶向蛋白降解(TPD)代表了一种很有前途的治疗方法,包括几种创新策略,包括但不限于靶向嵌合体(PROTACs),分子胶,疏水标签捆绑降解物(HyTTD)和靶向溶酶体嵌合体(LYTACs)。TPD的核心是小分子配体,它们在介导靶蛋白的降解中起着关键作用。本文综述了TPD小分子配体的研究现状。这些小分子配体可以利用蛋白酶体、溶酶体、自噬或疏水标记系统来实现靶蛋白的降解。本文主要介绍了它们的设计原则、应用优势和潜在的局限性。并对TPD技术的发展前景和未来发展方向进行了简要讨论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
11.70
自引率
9.00%
发文量
863
审稿时长
29 days
期刊介绍: The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信