Plasminogen activator inhibitor-1 inhibitors: a patent review (2006-present)

Introduction: Plasminogen activator inhibitor-1 (PAI-1), the serine protease inhibitor (serpin), binds to and inhibits the plasminogen activators-tissue-type plasminogen activator (tPA) and the urokinase-type plasminogen activator (uPA). This results in both a decrease in plasmin production and a decrease in the dissolution of fibrin clots. Elevated levels of PAI-1 are correlated with an increased risk for cardiovascular disease and have been linked to obesity and metabolic syndrome. Consequently, the pharmacological suppression of PAI-1 might prevent or treat vascular disease. Areas covered: This article provides an overview of the patenting activity on PAI-1 inhibitors. Patents filed by pharmaceutical companies or individual research groups are described, and the biological and biochemical evaluation of the inhibitors, including in vitro and in vivo studies, is discussed. An overview of patents pertaining to using these inhibitors for treating various diseases is also included. Expert opinion: Although there is still no PAI-1 inhibitor being evaluated in a clinical setting or approved for human therapy, research in this field has progressed, and promising new compounds have been designed. Most research has focused on improving the pharmacological profile of these compounds, which will hopefully allow them to proceed to clinical studies. Despite the need for further testing and research, the potential use of PAI-1 inhibitors for treating cardiovascular disease appears quite promising.