Department of Organic Chemistry, Faculty of Chemistry, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Department of Chemical and Bioprocesses Engineering, School of Engineering, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Curr Med Chem. 2019;26(17):3175-3200. doi: 10.2174/0929867325666180125165340.
Factor Xa (FXa) plays a key role in haemostasis, it is a central part of the blood coagulation cascade which catalyzes the production of thrombin and leads to clot formation and wound closure. Therefore, FXa is an attractive target for the development of new anticoagulant agents. In this review, we will first describe the molecular features of this fundamental protein in order to understand its mechanism of action, an essential background for the design of novel inhibitors by means of synthetic organic chemistry or using peptides obtained from recombinant methodologies. Then, we will review the current state of the synthesis of novel direct FXa inhibitors along with their mechanisms of action. Finally, approved reversal agents that aid in maintaining blood haemostasis by using these commercial drugs will also be discussed.
Xa 因子 (FXa) 在止血中起着关键作用,它是血液凝血级联反应的核心部分,可催化凝血酶的产生,导致血栓形成和伤口闭合。因此,FXa 是开发新型抗凝剂的有吸引力的靶点。在这篇综述中,我们将首先描述这种基本蛋白质的分子特征,以了解其作用机制,这是通过合成有机化学或使用重组方法获得的肽设计新型抑制剂的必要背景。然后,我们将回顾新型直接 FXa 抑制剂的合成现状及其作用机制。最后,还将讨论使用这些商业药物来帮助维持血液止血的批准的逆转剂。