Progress in the Preclinical Discovery and Clinical Development of Class I and Dual Class I/IV Phosphoinositide 3-kinase (PI3K) Inhibitors

Curr Med Chem. 2011;18(18):2686-714. doi: 10.2174/092986711796011229.

Abstract

The phosphoinositide 3-kinases (PI3Ks) constitute an important family of lipid kinase enzymes that control a range of cellular processes through their regulation of a network of signal transduction pathways, and have emerged as important therapeutic targets in the context of cancer, inflammation and cardiovascular diseases. Since the mid-late 1990s, considerable progress has been made in the discovery and development of small molecule ATP-competitive PI3K inhibitors, a number of which have entered early phase human trials over recent years from which key clinical results are now being disclosed. This review summarizes progress made to date, primarily on the discovery and characterization of class I and dual class I/IV subtype inhibitors, together with advances that have been made in translational and clinical research, notably in cancer.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / enzymology
  • Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors*
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Clinical Medicine / methods*
  • Clinical Medicine / trends
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / enzymology
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Protein Kinase Inhibitors
  • Class I Phosphatidylinositol 3-Kinases