title: Small-molecule inhibitors of the PI3K signaling network.
abstract: The phosphoinositide 3-kinase (PI3K) signaling pathway controls a wide variety of cellular processes including cell death and survival, cell migration, protein synthesis and metabolism. Aberrant PI3K-dependent signaling, mediated by Akt kinase, has been implicated in many human diseases including cancer, inflammation, cardiovascular disease and metabolic diseases, making this pathway a principle target for drug development. In this article we will summarize the PI3K signaling network and discuss current strategies for pathway inhibition. We will also explore the importance and emerging relevance of Akt-independent PI3K signaling pathways and discuss attempts being made to harness these pathways by inhibiting the binding of a product of PI3K, phosphatidylinositol-(3,4,5)-trisphosphate, to effector pleckstrin homology domains.
authors.affiliation: Department of biochemistry, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA.
authors.forename: Colleen R
authors.initials: CR
authors.lastname: McNamara
authors.forename: Alexei
authors.initials: A
authors.lastname: Degterev
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D054852:Small Molecule Libraries