Targeting the p53-MDM2 interaction to treat cancer.
Targeting the p53-MDM2 interaction to treat cancer.
复制标题
针对P53-MDM2相互作用以治疗癌症。
DOI：
10.1038/sj.bjc.6602164
复制
发表时间：
2004-10-18
影响因子：
8.8
通讯作者：
Vassilev, LT
中科院分区：
文献类型：
--
作者：
Klein, C;Vassilev, LT
肿瘤抑制因子p53是一种具有强大抗肿瘤活性的转录因子，通过反馈机制由其负调节因子MDM 2（小鼠双微体2，在人类中也称为HDM 2）控制。MDM 2在许多肿瘤中过量产生，它结合p53并通过调节其转录活性和稳定性来抑制其功能。通过抑制p53与MDM 2的物理相互作用来激活肿瘤细胞中的p53一直是癌症药物发现的焦点。然而，非肽MDM 2拮抗剂的开发变得具有挑战性。最近，已经鉴定了MDM 2的第一种有效的和选择性的小分子拮抗剂Nutlins。Nutlin的研究为靶向p53-MDM 2相互作用用于癌症治疗提供了体外和体内原理验证。
The tumour suppressor p53 is a transcription factor with powerful antitumour activity that is controlled by its negative regulator MDM2 (mouse double minute 2, also termed HDM2 in humans) through a feedback mechanism. MDM2, which is overproduced in many tumours, binds p53 and inhibits its function by modulating its transcriptional activity and stability. Activation of p53 in tumour cells by inhibiting its physical interaction with MDM2 has been in the focus of cancer drug discovery. However, development of nonpeptidic MDM2 antagonists turned out to be challenging. Recently, the first potent and selective small-molecule antagonists of MDM2, the Nutlins, have been identified. Studies with Nutlins provided in vitro and in vivo proof-of-principle for targeting p53–MDM2 interaction for cancer therapy.
登录
查看更多内容
影响因子：
8
作者：
Blaydes, JP;Gire, V;WynfordThomas, D
通讯作者：
WynfordThomas, D
影响因子：
5.6
作者：
Bottger, A;Bottger, V;Lane, DP
通讯作者：
Lane, DP
影响因子：
5.6
作者：
Chène, P;Fuchs, J;Fabbro, D
通讯作者：
Fabbro, D
影响因子：
7.3
作者：
García-Echeverría, C;Chène, P;Furet, P
通讯作者：
Furet, P
影响因子：
9.2
作者：
Bottger, A;Bottger, V;Lane, DP
通讯作者：
Lane, DP