PI3Ks-drug targets in inflammation and cancer

Subcell Biochem. 2012;58:111-81. doi: 10.1007/978-94-007-3012-0_5.

Abstract

Phosphoinositide 3-kinases (PI3Ks) control cell growth, proliferation, cell survival, metabolic activity, vesicular trafficking, degranulation, and migration. Through these processes, PI3Ks modulate vital physiology. When over-activated in disease, PI3K promotes tumor growth, angiogenesis, metastasis or excessive immune cell activation in inflammation, allergy and autoimmunity. This chapter will introduce molecular activation and signaling of PI3Ks, and connections to target of rapamycin (TOR) and PI3K-related protein kinases (PIKKs). The focus will be on class I PI3Ks, and extend into current developments to exploit mechanistic knowledge for therapy.

Publication types

  • Review

MeSH terms

  • Autoimmunity / drug effects
  • Autoimmunity / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Diglycerides / metabolism
  • Enzyme Inhibitors / pharmacology
  • Eukaryotic Cells / enzymology*
  • Eukaryotic Cells / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypersensitivity / drug therapy
  • Hypersensitivity / enzymology*
  • Hypersensitivity / genetics
  • Hypersensitivity / pathology
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / classification
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / classification
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Second Messenger Systems*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Diglycerides
  • Enzyme Inhibitors
  • Isoenzymes
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphoinositide-3 Kinase Inhibitors
  • Inositol 1,4,5-Trisphosphate
  • MTOR protein, human
  • TOR Serine-Threonine Kinases