title: Small molecules inhibitors of plasminogen activator inhibitor-1 - an overview.
abstract: 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.
authors.affiliation: Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Rouch
authors.affiliation: Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Vanucci-Bacqué
authors.affiliation: Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France. Electronic address: bedos@chimie.ups-tlse.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Bedos-Belval
authors.affiliation: Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France. Electronic address: baltas@chimie.ups-tlse.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Baltas
mesh_terms: D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D054852:Small Molecule Libraries
keywords: Cardiovascular diseases; Fibrinolysis; Inhibitors; Plasminogen activator inhibitor (PAI-1); Tissue-type plasminogen activator (tPA); Urokinase plasminogen activator (uPA)