期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 64, 期 15, 页码 10621-10640出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c00940
关键词
-
资金
- National Natural Science Foundation of China [82073682, 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
This study summarized inhibitors of MDM4/p53 interactions, including small molecules and peptide-based compounds. Recent research suggests that concurrent inhibition of MDM4 and MDM2 might be more beneficial than only targeting MDM2, providing a reference for further development of MDM4 inhibitors.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据