Bradykinin receptor ligands: therapeutic perspectives

The kallikrein–kinin system consists of the precursor kininogens, the proteolytic kallikrein enzymes, the kinin peptides (which are produced through cleavage of kininogens by kallikreins) and two G-protein-coupled receptors (GPCRs), termed the B1 and B2 receptors, that mediate the biological effects of kinin peptides.The growing knowledge of the biological role of kinins has fuelled the development of potent and selective kinin receptor modulators as potential therapeutics.This medicinal chemistry effort, which was initiated with peptides in the 1970s, has now culminated in the production of a number of novel non-peptide antagonists, some of which are awaiting clinical trials.This article provides an overview of the kinin biology that is relevant to the roles of kinins in disease, and then considers the potential of kinin receptor modulators in various disease indications, including inflammation and pain.