Discovery and development of plasma kallikrein inhibitors for multiple diseases.


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.


Factor XI,Hereditary angioedema,Plasma kallikrein inhibitor,Selectivity,Structure activity relationship,

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