Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, Hefei University of Technology, Hefei, Anhui, 230009, PR China; School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, 230009, PR China. Electronic address: [Email]
Plasma kallikrein (PKal) belongs to the family of trypsin-like serine proteases. The expression of PKal is associated with multiple physiological systems or pathways such as coagulation pathway, platelet aggregation process, kallikrein-kinin system, renin-angiotensin system and complement pathway. On the basis of PKal's multiple physiological functions, it has been considered as a potential target for several diseases including hereditary angioedema, microvascular complications of diabetes mellitus and cerebrovascular disease. Up to now, many PKal inhibitors have been identified and a few of them have reached clinical trials or market. This review summarizes the development of small molecule and peptide PKal inhibitors having different scaffolds and discusses their structure-activity relationship and selectivity. We hope this review facilitates a comprehensive understanding of the types of PKal inhibitors developed to tackle different manifestations of PKal-associated diseases.