Small molecules inhibitors of plasminogen activator inhibitor-1 - an overview

Eur J Med Chem. 2015 Mar 6;92:619-36. doi: 10.1016/j.ejmech.2015.01.010. Epub 2015 Jan 8.


PAI-1, a glycoprotein from the serpin family and the main inhibitor of tPA and uPA, plays an essential role in the regulation of intra and extravascular fibrinolysis by inhibiting the formation of plasmin from plasminogen. PAI-1 is also involved in pathological processes such as thromboembolic diseases, atherosclerosis, fibrosis and cancer. The inhibition of PAI-1 activity by small organic molecules has been observed in vitro and with some in vivo models. Based on these findings, PAI-1 appears as a potential therapeutic target for several pathological conditions. Over the past decades, many efforts have therefore been devoted to developing PAI-1 inhibitors. This article provides an overview of the publishing activity on small organic molecules used as PAI-1 inhibitors. The chemical synthesis of the most potent inhibitors as well as their biological and biochemical evaluations is also presented.

Keywords: Cardiovascular diseases; Fibrinolysis; Inhibitors; Plasminogen activator inhibitor (PAI-1); Tissue-type plasminogen activator (tPA); Urokinase plasminogen activator (uPA).

Publication types

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

MeSH terms

  • Humans
  • Models, Molecular
  • Molecular Structure
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*


  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Small Molecule Libraries