title: Recent developments of small molecule PI3K/mTOR dual inhibitors.
abstract: 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 phosphoinositidedependent 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).
authors.forename: Yan-Na
authors.initials: YN
authors.lastname: Liu
authors.forename: Ren-Zhong
authors.initials: RZ
authors.lastname: Wan
authors.affiliation: Department of Organic Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, P.R. China. liuzhaop@sdu.edu.cn.
authors.forename: Zhao-Peng
authors.initials: ZP
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D058570:TOR Serine-Threonine Kinases