Novel or expanding current targets in fibrinolysis

Drug Discov Today. 2014 Sep;19(9):1476-82. doi: 10.1016/j.drudis.2014.05.025. Epub 2014 Jun 2.

Abstract

Globally the leading cause of long-term disability and mortality stems from cardiovascular diseases, which creates an enormous economic burden. Currently available treatments for intravascular thrombosis consist of a large repertoire of antithrombotic agents targeting coagulation and platelet function. However, the only agents available to enhance fibrinolysis are recombinant or modified forms of plasminogen activators. Their clinical use is limited by low efficacy, life-threatening side-effects (primarily caused by the high systemic dose required) and the inapplicability for prophylactic use. This review provides an update on the latest advances in targeting the antifibrinolytic proteins, plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, and will highlight novel therapeutic avenues to enhance fibrinolysis.

Publication types

  • Review

MeSH terms

  • Animals
  • Carboxypeptidase B2 / drug effects
  • Carboxypeptidase B2 / metabolism
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / physiopathology
  • Drug Design*
  • Fibrinolysis / drug effects*
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / pharmacology*
  • Humans
  • Molecular Targeted Therapy
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Thrombosis / drug therapy
  • Thrombosis / physiopathology

Substances

  • Fibrinolytic Agents
  • Plasminogen Activator Inhibitor 1
  • Carboxypeptidase B2