Targeting the MDM2-p53 interaction for cancer therapy.
Targeting the MDM2-p53 interaction for cancer therapy.
复制标题
DOI：
10.1158/1078-0432.ccr-07-5136
复制
发表时间：
2008-09-01
期刊：
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Shangary S;Wang S
p53是一种强大的肿瘤抑制因子，并且是一种有吸引力的癌症治疗靶点，因为它可以被功能性激活以根除肿瘤。编码p53蛋白的基因在一半的人类癌症中突变或缺失，这使其肿瘤抑制活性失活。在具有野生型p53状态的其余癌症中，其功能通过与人鼠双微体2（MDM 2）癌蛋白的直接相互作用而被有效抑制。阻断MDM 2-p53相互作用以重新激活p53功能是一种有前途的癌症治疗策略。本文将重点介绍作为癌症治疗方法的MDM 2-p53相互作用的小分子抑制剂的设计和开发进展。
p53 is a powerful tumor suppressor and is an attractive cancer therapeutic target because it can be functionally activated to eradicate tumors. The gene encoding p53 protein is mutated or deleted in half of human cancers, which inactivates its tumor suppressor activity. In the remaining cancers with wild-type p53 status, its function is effectively inhibited through direct interaction with the human murine double minute 2 (MDM2) oncoprotein. Blocking the MDM2-p53 interaction to reactivate the p53 function is a promising cancer therapeutic strategy. This review will highlight the advances in the design and development of small-molecule inhibitors of the MDM2-p53 interaction as a cancer therapeutic approach.