标题：Recent Developments of Small Molecule PI3K/mTOR Dual Inhibitors
作者：Liu, Yan-Na; Wan, Ren-Zhong; Liu, Zhao-Peng
作者机构：[Liu, Yan-Na; Liu, Zhao-Peng] Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Organ Chem,Key Lab Chem Biol, Jinan 250012, Peoples R China.; [Wa 更多
通讯作者地址：[Liu, ZP]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Organ Chem,Key Lab Chem Biol, Jinan 250012, Peoples R China.
来源：MINI-REVIEWS IN MEDICINAL CHEMISTRY
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
摘要：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).