{"title":"Recent advances in developing targeted protein degraders","authors":"Binbin Cheng, Hongqiao Li, Xiaopeng Peng, Jianjun Chen, Chuxiao Shao, Zhihua Kong","doi":"10.1016/j.ejmech.2024.117212","DOIUrl":null,"url":null,"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.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"26 1","pages":""},"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://doi.org/10.1016/j.ejmech.2024.117212","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.
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.
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