中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Recent Progress and Clinical Development of Inhibitors that Block MDM4/p53 Protein-Protein Interactions

文献类型：期刊论文

作者Zhang, Shiyan1,2,3; Lou, Jianfeng1,2,3; Li, Yafang2,3,4; Zhou, Feilong2,3; Yan, Ziqin2,3; Lyu, Xilin2,3; Zhao, Yujun1,2,3,5
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2021-08-12
卷号64期号:15页码:10621-10640
ISSN号0022-2623
DOI10.1021/acs.jmedchem.1c00940
通讯作者Zhao, Yujun(yjzhao@simm.ac.cn)
英文摘要MDM4 is a homologue of MDM2, serving cooperatively as the negative regulator of tumor suppressor p53. Under the shadow of MDM2 inhibitors, limited efforts had been put into the discovery of MDM4 modulators. Recent studies of the experimental drug ALRN-6924, a dual MDM4 and MDM2 inhibitor, suggest that concurrent inhibition of MDM4 and MDM2 might be beneficial over only MDM2 inhibition. In view of the present research progress, we summarized published inhibitors of MDM4/p53 interactions including both peptide-based compounds and small molecules. Cocrystal structures of ligand/ MDM4 complexes have been examined, and their structural features were compiled and compared in order to show the molecular basis required for high MDM4 binding affinities. Representative examples of small-molecule MDM4 inhibitors were discussed, followed by clinical results of ALRN-6924, together, providing a consolidated reference for further development of MDM4 inhibitors, either dual or selective.
WOS关键词HDMX-MEDIATED SUPPRESSION ; DOUBLE MINUTE 2 ; SMALL-MOLECULE ; P53 PATHWAY ; HUMAN MDM2 ; STAPLED P53 ; DISCOVERY ; POTENT ; IDENTIFICATION ; ACTIVATION
资助项目National Natural Science Foundation of China[82073682] ; National Natural Science Foundation of China[81872724] ; National Major Science & Technology Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-004-010] ; Science and Technology Commission of Shanghai Municipality[18431907100] ; K. C. Wong Education Foundation
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000685644300008
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/297654]  
专题新药研究国家重点实验室
通讯作者Zhao, Yujun
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Small Mol Drug Res Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Univ Sci & Technol China, Nano Sci & Technol Inst, Suzhou 215123, Jiangsu, Peoples R China
5.Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Shiyan,Lou, Jianfeng,Li, Yafang,et al. Recent Progress and Clinical Development of Inhibitors that Block MDM4/p53 Protein-Protein Interactions[J]. JOURNAL OF MEDICINAL CHEMISTRY,2021,64(15):10621-10640.
APA Zhang, Shiyan.,Lou, Jianfeng.,Li, Yafang.,Zhou, Feilong.,Yan, Ziqin.,...&Zhao, Yujun.(2021).Recent Progress and Clinical Development of Inhibitors that Block MDM4/p53 Protein-Protein Interactions.JOURNAL OF MEDICINAL CHEMISTRY,64(15),10621-10640.
MLA Zhang, Shiyan,et al."Recent Progress and Clinical Development of Inhibitors that Block MDM4/p53 Protein-Protein Interactions".JOURNAL OF MEDICINAL CHEMISTRY 64.15(2021):10621-10640.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。