Advancements in Serine Protease Inhibitors: From Mechanistic Insights to Clinical Applications

Serine proteases, a significant class of enzymes comprising approximately one-third of known human proteases, are ubiquitously present across various organisms. These enzymes typically exhibit highly conserved catalytic domain structures, and their activity is stringently regulated within the body, playing a pivotal role in numerous physiological processes. Dysregulation of serine protease activity can result in severe consequences, including excessive inflammation, heightened risk of thrombosis and cancer, and even mortality. Serine protease inhibitors have emerged as critical regulators, offering a broad range of physiological functions such as maintaining the coagulation–fibrinolysis balance, modulating inflammatory responses, accelerating wound healing, promoting apoptosis, and providing antitumor and antiviral effects. As a result, the development of serine protease inhibitors has become increasingly vital. In recent years, significant progress in the study of serine proteases has led to the pivotal role of various serine protease inhibitors in clinical diagnosis and treatment. This review explores the fundamental mechanisms of serine protease inhibitors, summarizes those that have been successfully integrated into clinical practice, and discusses the challenges encountered in their development along with partial solutions. These advancements lay the groundwork for further refinement and innovation in serine protease inhibitor therapeutics.