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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2015, Vol. 35 Issue (9): 78-84    DOI: 10.13523/j.cb.20150912
综述     
Mdm2/MdmX抑制剂
覃凌云, 陈蓉, 苏正定
湖北工业大学生物工程学院 湖北省工业发酵协同创新中心 教育部发酵工程重点实验室 武汉 430068
Design of Mdm2/MdmX Inhibitors
QIN Ling-yun, CHEN Rong, SU Zheng-ding
Department of Biotechnology, Hubei Collaborative Innovation Center for Industrial Fermentation, Key Laboratory of Industrial Fermentation of Ministry of Education, Hubei University of Technology, Wuhan 430068, China
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摘要:

Mdm2 (murine double minute 2,又称为Hdm2)和MdmX (murine double minute X,又称为Hdm4) 的异常过表达与近半数的癌症直接相关,设计靶向Mdm2/MdmX-p53蛋白质相互作用位点抑制剂,解除Mdm2和MdmX对p53的抑制作用有着重要的临床意义.尽管Mdm2和MdmX结构非常相似,但仅有Mdm2小分子抑制剂的筛选和设计研究较深入.对依据nutlin分子构效关系、结构生物学、组合化学多重优化等手段筛设计MdmX抑制剂的研究进展进行简述,并讨论天然产物库在筛选MdmX/Mdm2抑制剂新型结构框架的应用前景.

关键词: p53MdmX抑制剂药物设计天然产物    
Abstract:

Inhibition of p53 by abnormaloverexpression of Mdm2 (murine double minute 2, also known as Hdm2) and MdmX (murine double minute X, also known as Hdm4) is relevant to nearly half of cancers. Thereby it is clinically profound that the removal of the inhibition of Mdm2/MdmX to p53 by designing Mdm2/MdmX-specific inhibitors. Structurally Mdm2 and MdmX are similar to each other, but the discovery of Mdm2 inhibitor has so far made advanced progress compared to the design of MdmX inhibitors. The progress on the design of MdmX inhibitors based on the structure-activity relationships of nutlins (Mdm2 inhibitors), structural biology and combinatorial chemistry were reviewed. The potential application of natural compounds is discussed for searching novel scaffolds of Mdm2/MdmX inhibitors.

Key words: p53    MdmX inhibitors    Drug design    Natural compounds
收稿日期: 2015-04-22 出版日期: 2015-09-25
ZTFLH:  Q816  
通讯作者: 苏正定     E-mail: zhengdingsu@mail.hbut.edu.cn
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引用本文:

覃凌云, 陈蓉, 苏正定. Mdm2/MdmX抑制剂[J]. 中国生物工程杂志, 2015, 35(9): 78-84.

QIN Ling-yun, CHEN Rong, SU Zheng-ding. Design of Mdm2/MdmX Inhibitors. China Biotechnology, 2015, 35(9): 78-84.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20150912        https://manu60.magtech.com.cn/biotech/CN/Y2015/V35/I9/78


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