Anticancer strategies by upregulating p53 through inhibition of its ubiquitination by MDM2

被引：17

作者：

Anifowose, Abiodun ^{[1
,2
]}

Agbowuro, Ayodeji A. ^{[1
,2
]}

Yang, Xiaoxiao ^{[1
,2
]}

Wang, Binghe ^{[1
,2
]}

机构：

[1] Georgia State Univ, Dept Chem, Petit Sci Ctr, 100 Piedmont Ave, Atlanta, GA 30303 USA

[2] Georgia State Univ, Ctr Diagnost & Therapeut, Petit Sci Ctr, 100 Piedmont Ave, Atlanta, GA 30303 USA

来源：

MEDICINAL CHEMISTRY RESEARCH | 2020年 / 29卷 / 07期

基金：

美国国家卫生研究院;

关键词：

p53; MDM2; Small-molecule inhibitors; restoration; STRUCTURE-BASED DESIGN; TARGETED PROTEIN-DEGRADATION; SMALL-MOLECULE RITA; CELL-CYCLE ARREST; TRANSCRIPTIONAL ACTIVATION; STAPLED P53; CANCER; APOPTOSIS; DOMAIN; DISCOVERY;

D O I：

10.1007/s00044-020-02574-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The potentiation of p53 activity through inhibition of its negative regulator MDM2 is an attractive strategy for anticancer therapy. Much progress has been made in the last decade in a diverse range of areas related to p53 and MDM2. This review focuses on the recent progress in developing small-molecule inhibitors of the MDM2 protein by covering the following approaches that inhibit the function of the p53-MDM2 axis: (1) direct binding to MDM2, (2) direct binding to p53, (3) targeted degradation of MDM2 by the PROTAC approach, and (4) inhibition of MDM2/MDM4 interaction. Given the importance of p53 in cancer development, we hope that research in this area will lead to anticancer drugs in the not too distant future.

引用

页码：1105 / 1121

页数：17

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