Dual inhibitors of PI3K/mTOR or mTOR-selective inhibitors: Which way shall we go?

D. A. Sabbah, M. G. Brattain, H. Zhong

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


The phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway is a central regulator in cell proliferation, growth, and angiogenesis. Inhibition of this pathway therefore is a major strategy for cancer chemotherapy. In order to induce the maximal therapeutic outcome in cancer treatment, vertical inhibition of the PI3K/AKT/mTOR pathway or horizontal inhibition of PI3K/AKT/mTOR and other kinases has been reported. In this review, we discuss the drug design and clinical development of dual inhibitors of PI3K and mTOR as well as the mTOR-selective inhibitors, classified based on the mechanism of action and the chemical structures. Structural determinants for increasing selectivity toward PI3Kα or mTOR are revealed from the structure-activity relationship of the reported inhibitors. Current clinical development in combination therapy of inhibitors involving in the PI3K/AKT/mTOR pathway is also discussed.

Original languageEnglish (US)
Pages (from-to)5528-5544
Number of pages17
JournalCurrent medicinal chemistry
Issue number36
StatePublished - Dec 2011


  • And cancer
  • Kinase inhibitors
  • PI3Kα
  • Rapamycin
  • Selectivity
  • mTORC1
  • mTORC2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


Dive into the research topics of 'Dual inhibitors of PI3K/mTOR or mTOR-selective inhibitors: Which way shall we go?'. Together they form a unique fingerprint.

Cite this