Structure, Function and Inhibition of the Phosphoinositide 3-kinase p110α Enzyme

Biochem Soc Trans. 2014 Feb;42(1):120-4. doi: 10.1042/BST20130255.

Abstract

The PI3K (phosphoinositide 3-kinase) p110α isoform is activated by oncogenic mutations in many cancers. This has stimulated intense interest in identifying inhibitors of the PI3K pathway as well as p110α-selective inhibitors, and understanding the mechanisms underlying activation by the oncogenic mutations. In the present article, we review recent progress in the structure and function of the p110α enzyme and two of its most common oncogenic mutations, the development of isoform-selective inhibitors, and p110α pharmacology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Catalytic Domain
  • Class I Phosphatidylinositol 3-Kinases
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry
  • Isoenzymes / physiology
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Phosphatidylinositol 3-Kinases / chemistry*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors

Substances

  • Antineoplastic Agents
  • Isoenzymes
  • Phosphoinositide-3 Kinase Inhibitors
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human