P53 Mdm2 Inhibitors

被引：33
|
作者：
Khoury, Kareem
Doemling, Alex [1 ]
机构：
[1] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA
来源：
CURRENT PHARMACEUTICAL DESIGN | 2012年 / 18卷 / 30期
基金：
美国国家科学基金会;
关键词：
p53; MDM2; HDM2; protein protein interactions; small molecule inhibitors; IN-VITRO; PROTEIN; ANTAGONISTS; COMPLEX; 1,4-BENZODIAZEPINE-2,5-DIONES; OVEREXPRESSION; AMPLIFICATION; DISCOVERY; TUMORS; LEADS;
D O I：
10.2174/138161212802651580
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The protein-protein interaction (PPI) between p53 and its negative regulator MDM2 comprises one of the most important and intensely studied PPI's involved in preventing the initiation of cancer. The interaction between p53 and MDM2 is conformation-based and is tightly regulated on multiple levels. Due to the Angstrom level structural insight there is a reasonable understanding of the structural requirements needed for a molecule to bind to MDM2 and successfully inhibit the p53/MDM2 interaction. The current review summarizes the binding characteristics of the different disclosed small molecules for inhibition of MDM2 with a co-crystal structure. Synthetic access to these compounds as well as their derivatives are described in detail.
引用
收藏
页码：4668 / 4678
页数：11
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