Review
Version 2
Preserved in Portico This version is not peer-reviewed
Drugs of the Kallikrein-Kinin System: An Overview
Version 1
: Received: 12 May 2023 / Approved: 15 May 2023 / Online: 15 May 2023 (09:40:56 CEST)
Version 2 : Received: 3 June 2023 / Approved: 6 June 2023 / Online: 6 June 2023 (09:42:29 CEST)
Version 2 : Received: 3 June 2023 / Approved: 6 June 2023 / Online: 6 June 2023 (09:42:29 CEST)
A peer-reviewed article of this Preprint also exists.
Marceau, F. Drugs of the Kallikrein–Kinin System: An Overview. Drugs Drug Candidates 2023, 2, 538-553. Marceau, F. Drugs of the Kallikrein–Kinin System: An Overview. Drugs Drug Candidates 2023, 2, 538-553.
Abstract
Abstract: The kallikrein-kinin system consists of the two kininogen substrates, present in blood plasma, and of two serine proteases, the plasma and tissue kallikreins. The action of the latter on kininogens produce small peptides, the kinins, short lived but endowed by powerful pharmacologic actions on blood vessels and other tissues. Many recent and exciting therapeutic developments in the field are briefly summarized. Notably, various novel strategies are being clinically developed to inhibit the formation of bradykinin or block its receptors in the management of hereditary angioedema. The interventions include orally bioavailable drugs, biotechnological proteins, and gene therapy. These approaches are currently explored in a variety of other inflammatory and thrombotic disorders. Harnessing controlled kinin formation is also of potential therapeutic interest as shown by the clinical development of recombinant tissue kallikrein for ischemic stroke and renal disease. Biomarkers of a kinin-mediated disorders, frequently implicating edemas, include the consumption of kininogen(s), plasma kallikrein activity, and the detection of circulating kinin metabolites such as fragments BK1-5 and BK2-9. Novel opportunities to clinically apply the underexploited drugs of the kallikrein-kinin system are briefly reviewed. This personal perspective is offered by an observer of, and a participant in drug characterization during the last 4 decades.
Keywords
kallikrein-kinin system; kininogens; bradykinin; B1 receptor; B2 receptor; hereditary angioedema
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Commenter: François Marceau
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