期刊
MINI-REVIEWS IN MEDICINAL CHEMISTRY
卷 13, 期 14, 页码 2047-2059出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/13895575113136660105
关键词
Anticancer; anticancer agents; cancer; dual PI3K/mTOR kinase inhibitors; kinase inhibitors; PI3K; PI3K alpha; PI3K/Akt/mTOR; PI3K signaling pathway; mTOR; structure-activity relationships; SARs
资金
- Shandong Provincial Natural Science Foundation [ZR2011CZ001]
The phosphoinositide 3-kinases (PI3Ks) are lipid kinases that play a central role in control of cell growth, proliferation, migration, survival and angiogenesis, and drive the progression of tumors by activating phosphoinositide-dependent kinase, protein kinase B (Akt) and the mammalian target of rapamycin (mTOR). The PI3K/Akt/mTOR pathway has been shown to play an important role in cancer and has become an important target for anticancer drug development. An interest in targeting two important points along this critical signaling pathway has spurred the development of dual PI3K/mTOR inhibitors that could both prevent cancer cell proliferation and induce programmed cell death (apoptosis) by fully suppressing Akt activation. This review summarizes the developments of a diversity of small molecule dual PI3K/mTOR inhibitors in recent 10 years, with an emphasis on their structural features, the relevant biological activities, and the structure-activity relationships (SARs).
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