| 引用本文: | 谢妙红,高明明,凌佳楠,杜文婷.小分子蛋白降解靶向嵌合体的研究进展[J].中国现代应用药学,2021,38(22):2891-2899. |
| XIE Miaohong,GAO Mingming,LING Jianan,DU Wenting.Research Progress on Small-molecule Proteolytic Targeting Chimera[J].Chin J Mod Appl Pharm(中国现代应用药学),2021,38(22):2891-2899. |
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| 摘要: |
| 蛋白降解靶向嵌合体（proteolytic targeting chimera，PROTAC）是一种通过泛素-蛋白酶体系统选择性降解靶蛋白的新技术。PROTAC是一类异双功能分子，其中包含靶向目标蛋白质的配体，募集E3连接酶的配体和连接这2个配体的接头。与传统抑制剂相比，它们在功效、选择性和耐药性方面均具有许多优势。因此，近二十年来已经开发了许多有前途的PROTACs，尤其是小分子PROTACs。本文选择CRBN、VHL、MDM2和cIAP1 4种常见E3连接酶为代表，针对不同的靶向目标进行分类，在阐述4种E3连接酶各自特点的同时，也综述了基于不同E3连接酶的小分子PROTACs的研究进展。 |
| 关键词: E3连接酶 蛋白降解靶向嵌合体 蛋白降解 小分子抑制剂 癌症治疗 |
| DOI：10.13748/j.cnki.issn1007-7693.2021.22.024 |
| 分类号:R914.2 |
| 基金项目:浙江省自然科学基金项目（LY21H300003）；国家级大学生创新创业训练计划项目（202113023007） |
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| Research Progress on Small-molecule Proteolytic Targeting Chimera |
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XIE Miaohong, GAO Mingming, LING Jianan, DU Wenting
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Hangzhou Medical College, Hangzhou 310053, China
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| Abstract: |
| Proteolytic-targeting chimera(PROTAC) is a new technology to selectively degrade target proteins via ubiquitin-proteasome system. PROTACs are a class of heterobifunctional molecules, which contain a ligand targeting the protein of interest, a ligand recruiting an E3 ligase and a linker connecting these two ligands. Comapred with traditional inhibitor, they provide several advantages in potency, selectivity and drug resistance. Thus, many promising PROTACs have been developed in the recent two decades, especially small-molecule PROTACs. This review selects 4 common E3 ligases, CRBN, VHL, MDM2 and cIAP1 as representatives, and classifies different target targets. It also summarizes the progress of small-molecule PROTACs based on different E3 ligases while describing the characteristics of these four E3 ligases. |
| Key words: E3 ligases PROTACs protein degradation small-molecule inhibitors anticancer |
