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  • Title: Discovery and development of plasma kallikrein inhibitors for multiple diseases.
    Author: Xie Z, Li Z, Shao Y, Liao C.
    Journal: Eur J Med Chem; 2020 Mar 15; 190():112137. PubMed ID: 32066009.
    Abstract:
    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.
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