Small-molecule modulators of serine protease inhibitor proteins (serpins)

Serpins are a large, diverse, and well-studied family of proteins that regulate and control crucial physiological processes, such as inflammation (anti-trypsin, anti-chymotrypsin) [1], coagulation (antithrombin) [2], both thrombosis and thrombolysis (plasminogen activator inhibitor-1; PAI-1) [3], and immune responses (ovalbumin serpin). There are 37 serpins encoded in the human genome, classified in nine clades (Box 1). Thirty of Serine protease inhibitors (serpins) are a large family of proteins that regulate and control crucial physiological processes, such as inflammation, coagulation, thrombosis and thrombolysis, and immune responses. The extraordinary impact that these proteins have on numerous crucial pathways makes them an attractive target for drug discovery. In this review, we discuss recent advances in research on small-molecule modulators of serpins, examine their mode of action, analyse the structural data from crystallised protein?ligand complexes, and highlight the potential obstacles and possible therapeutic perspectives. The application of in silico methods for rational drug discovery is also summarised. In addition, we stress the need for continued research in this field.

Automated summary

Serpins, a large and diverse family of proteins, play a crucial role in regulating inflammation, coagulation, thrombosis, thrombolysis, and immune responses. Recent advances in research on small-molecule modulators of serpins, their mode of action, and potential therapeutic perspectives are discussed, highlighting the importance of continued research in this field.