Targeting the mTOR kinase domain: the second generation of mTOR inhibitors

被引:144
|
作者
Zhang, Yan-Jie [1 ]
Duan, Yanwen [2 ]
Zheng, X. F. Steven [1 ]
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Canc Inst New Jersey, Piscataway, NJ 08854 USA
[2] Hunan Engn Res Ctr Combinatorial Biosynth & Nat P, Changsha 410329, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; MAMMALIAN TARGET; RAPAMYCIN INHIBITOR; ANTITUMOR; NVP-BEZ235; GROWTH; POTENT; SURVIVAL; ACTIVATION; 3-KINASES;
D O I
10.1016/j.drudis.2011.02.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The mTOR signaling pathway is dysregulated in similar to 50% of all human malignancies and is a major cancer drug target. Although rapamycin analogs (rapalogs) have shown clinical efficacy in a subset of cancers, they do not fully exploit the antitumor potential of mTOR targeting. Because the mTOR kinase domain is important for rapamycin-sensitive and -insensitive functions, mTOR catalytic inhibitors have been developed recently as the second generation of anti-mTOR agents. Importantly, they have shown marked improvement of antitumor activity in vivo and in vitro. This review will detail the potential therapeutic value and issues of these novel antineoplastic agents, with emphasis placed on those that have already entered clinical trials.
引用
收藏
页码:325 / 331
页数:7
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