文献类型：期刊文献

英文题名：Biomacromolecule-mediated targeted protein degradation: an emerging strategy for cancer therapy

作者：Xi, Meiyang[1,2];Zhang, Fengxia[3];Zhu, Jingjing[3];Shen, Hualiang[1,2];Wu, Chunlei[1,2];Gao, Xiaozhong[2];Xu, Huiting[1,2];Wu, Yonghua[2];Shen, Runpu[1,2];Xia, Gang[3]

机构：[1]Shaoxing Univ, Zhejiang Engn Res Ctr Fat Soluble Vitamin, Shaoxing 312000, Peoples R China;[2]Shaoxing Univ, Coll Chem & Chem Engn, Shaoxing 312000, Peoples R China;[3]NovoCodex Biopharmaceut Co Ltd, Shaoxing 312090, Peoples R China

年份：2025

卷号：298

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：SCI-EXPANDED(收录号：WOS:001545020900001)、、Scopus(收录号：2-s2.0-105012214308)、WOS

基金：The authors greatly acknowledge the support from the National Natural Science Foundation of China (No. 22278270) .

语种：英文

外文关键词：Proteolysis targeting chimera (PROTAC); Biomacromolecule; Cancer therapy

外文摘要：Conventional cancer chemotherapeutics have long been confronted by significant challenges such as adverse effects and drug resistance. A target protein degradation technology, proteolysis targeting chimeras (PROTACs), emerges as a novel modality but with pharmacokinetic issues and toxicity limitations. In order to overcome limited permeability of PROTACs and minimize their on-target off-tumor toxicity in healthy tissues, various conjugates with biomacromolecules (antibodies or aptamers) have been engineered. Currently, several degraderantibody conjugates (DACs) have progressed to clinical trials for cancer therapy, while aptamer-PROTAC conjugates (APCs) and aptamer-based PROTACs with better tissue penetration and lower immunogenicity remain in the preclinical stage. In this review, we describe the mechanism of these conjugates, summarize their recent advances and discuss current challenges, trying to provide an insight into their development for targeted cancer therapy in future.