Selective and potent small-molecule inhibitors of PI3Ks

Future Med Chem. 2014 May;6(7):737-56. doi: 10.4155/fmc.14.28.


Class I PI3Ks are composed of four catalytic subunit variants (p110α, p110β, p110δ and p110γ). The PI3K pathway is among the most frequently activated pathways in many diseases, and has emerged as an attractive target for drug development, in particular for the treatment of many human cancers including breast, prostate, ovarian, gastric, colon and hepatocellular cancers. One of the challenges in the discovery of drugs that target kinases is designing small-molecule inhibitors that are sufficiently selective to minimize off-target activity and reduce the risk of potential toxicity. This review explores the current landscape of PI3K-selective inhibitor development and highlights recent advances in achieving selectivity for PI3Ks over other protein kinases, with an emphasis on available structural information.

Publication types

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

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Drug Discovery* / methods
  • Humans
  • Models, Molecular
  • Phosphatidylinositol 3-Kinases / chemistry
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*


  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Isoforms
  • Protein Kinase Inhibitors
  • Small Molecule Libraries