E3 ligase ligand optimization of Clinical PROTACs
文献类型：期刊论文
| 作者 | Jiang, Hanrui1,3; Xiong, Huan2,3; Gu, Shuang-Xi1; Wang, Mingliang2,3 |
| 刊名 | FRONTIERS IN CHEMISTRY
 |
| 出版日期 | 2023-01-17 |
| 卷号 | 11页码:15 |
| 关键词 | PROTACs E3 ubiquitin ligase ligand structure optimization clinical trials CRBN |
| ISSN号 | 2296-2646 |
| DOI | 10.3389/fchem.2023.1098331 |
| 通讯作者 | Gu, Shuang-Xi(shuangxigu@163.com) ; Wang, Mingliang(wangmingliang@simm.ac.cn) |
| 英文摘要 | Proteolysis targeting chimeras (PROTACs) technology can realize the development of drugs for non-druggable targets that are difficult to achieve with traditional small molecules, and therefore has attracted extensive attention from both academia and industry. Up to now, there are more than 600 known E3 ubiquitin ligases with different structures and functions, but only a few have developed corresponding E3 ubiquitin ligase ligands, and the ligands used to design PROTAC molecules are limited to a few types such as VHL (Von-Hippel-Lindau), CRBN (Cereblon), MDM2 (Mouse Doubleminute 2 homolog), IAP (Inhibitor of apoptosis proteins), etc. Most of the PROTAC molecules that have entered clinical trials were developed based on CRBN ligands, and only DT2216 was based on VHL ligand. Obviously, the structural optimization of E3 ubiquitin ligase ligands plays an instrumental role in PROTAC technology from bench to bedside. In this review, we review the structure optimization process of E3 ubiquitin ligase ligands currently entering clinical trials on PROTAC molecules, summarize some characteristics of these ligands in terms of druggability, and provide some preliminary insights into their structural optimization. We hope that this review will help medicinal chemists to develop more druggable molecules into clinical studies and to realize the greater therapeutic potential of PROTAC technology. |
| WOS关键词 | TARGETED PROTEIN-DEGRADATION ; RECEPTOR DEGRADING PROTAC ; HIGHLY POTENT ; RESISTANCE MECHANISMS ; HIF-ALPHA ; DISCOVERY ; BREAST ; COMPLEX ; SYSTEM ; IRAK4 |
| 资助项目 | Highlevel new RD institute[2019B090904008] ; High-level Innovative Research Institute[2021B0909050003] ; Department of Science and Technology of Guangdong Province |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000921242200001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/303385]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Gu, Shuang-Xi; Wang, Mingliang |
| 作者单位 | 1.Wuhan Inst Technol, Sch Chem Engn & Pharm, Key Lab Green Chem Proc, Minist Educ, Wuhan, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Hanrui,Xiong, Huan,Gu, Shuang-Xi,et al. E3 ligase ligand optimization of Clinical PROTACs[J]. FRONTIERS IN CHEMISTRY,2023,11:15. |
| APA | Jiang, Hanrui,Xiong, Huan,Gu, Shuang-Xi,&Wang, Mingliang.(2023).E3 ligase ligand optimization of Clinical PROTACs.FRONTIERS IN CHEMISTRY,11,15. |
| MLA | Jiang, Hanrui,et al."E3 ligase ligand optimization of Clinical PROTACs".FRONTIERS IN CHEMISTRY 11(2023):15. |
入库方式： OAI收割
来源：上海药物研究所
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