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.
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.
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.
PAI-1，丝氨酸蛋白酶抑制剂家族中的糖蛋白，是 tPA 和 uPA 的主要抑制剂，通过抑制纤溶酶原转化为纤溶酶，在调节血管内外纤维蛋白溶解中发挥重要作用。PAI-1 还参与血栓栓塞性疾病、动脉粥样硬化、纤维化和癌症等病理过程。在体外和一些体内模型中观察到小分子有机化合物对 PAI-1 活性的抑制作用。基于这些发现，PAI-1 似乎是多种病理状况的潜在治疗靶点。因此，在过去几十年中，人们付出了很多努力来开发 PAI-1 抑制剂。本文综述了用作 PAI-1 抑制剂的小分子有机化合物的出版活动。还介绍了最有效的抑制剂的化学合成及其生物学和生物化学评价。
