Discovery of a Potent and Selective Degrader for USP7
文献类型：期刊论文
| 作者 | Pei, Yuan1,3; Fu, Jingfeng1,3; Shi, Yunkai1,2; Zhang, Mengmeng1; Luo, Guanghao1,2,3; Luo, Xiaomin1,5 ; Song, Ning1,3; Mi, Tian1,3; Yang, Yaxi1,2,3; Li, Jia1,2,3,4,5
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| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
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| 出版日期 | 2022-08-15 |
| 卷号 | 61期号:33页码:e202204395 |
| 关键词 | Apoptotic Pathway Mutant p53 p53 Mutant Cancer Cells PROTAC USP7 Degrader |
| ISSN号 | 1433-7851 |
| DOI | 10.1002/anie.202204395 |
| 文献子类 | Article |
| 英文摘要 | The tumor suppressor p53 is the most frequently mutated gene in human cancer and more than half of cancers contain p53 mutations. The development of novel and effective therapeutic strategies for p53 mutant cancer therapy is a big challenge and highly desirable. Ubiquitin-specific protease 7 (USP7), also known as HAUSP, is a deubiquitinating enzyme and proposed to stabilize the oncogenic E3 ubiquitin ligase MDM2 that promotes the proteosomal degradation of p53. Herein, we report the design and characterization of U7D-1 as the first selective USP7-degrading Proteolysis Targeting Chimera (PROTAC). U7D-1 showed selective and effective USP7 degradation, and maintained potent cell growth inhibition in p53 mutant cancer cells, with USP7 inhibitor showing no activity. These data clearly demonstrated the practicality and importance of PROTAC as a preliminary chemical tool for investigating USP7 protein functions and a promising method for potential p53 mutant cancer therapy. |
| WOS关键词 | TARGETED PROTEIN-DEGRADATION ; MUTANT P53 ; WILD-TYPE ; INHIBITOR ; CANCER ; STABILIZATION ; HAUSP ; ACTIVATION ; LESSONS ; PROTACS |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000821522000001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309325]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Jia; Zhou, Yubo; Zhou, Bing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China; 3.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, Zhongshan Tsuihang New D 528400, Guangdong, Peoples R China; 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China |
| 推荐引用方式 GB/T 7714 | Pei, Yuan,Fu, Jingfeng,Shi, Yunkai,et al. Discovery of a Potent and Selective Degrader for USP7[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2022,61(33):e202204395. |
| APA | Pei, Yuan.,Fu, Jingfeng.,Shi, Yunkai.,Zhang, Mengmeng.,Luo, Guanghao.,...&Zhou, Bing.(2022).Discovery of a Potent and Selective Degrader for USP7.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,61(33),e202204395. |
| MLA | Pei, Yuan,et al."Discovery of a Potent and Selective Degrader for USP7".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 61.33(2022):e202204395. |
入库方式： OAI收割
来源：上海药物研究所
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