Kinins are peptide mediators exerting their pro-inflammatory actions by the selective stimulation of two distinct G-protein coupled receptors, termed BKB1R and BKB2R. While BKB2R is constitutively expressed in a multitude of tissues, BKB1R is hardly expressed at baseline but highly inducible by inflammatory mediators. In particular, BKB1R was shown to be involved in the pathogenesis of numerous inflammatory diseases. Areas covered: This review intends to evaluate the therapeutic potential of substances interacting with the BKB1R. To this purpose we summarize the published literature on animal studies with antagonists and knockout mice for this receptor. Expert Opinion: In most cases the pharmacological inhibition of BKB1R or its genetic deletion was beneficial for the outcome of the disease in animal models. Therefore, several companies have developed BKB1R antagonists and tested them in phase I and II clinical trials. However, none of the developed BKB1R antagonists was further developed for clinical use. We discuss possible reasons for this failure of translation of preclinical findings on BKB1R antagonists into the clinic.
Keywords: B1 receptor; B2 receptor; bradykinin; carboxypeptidase M; des-Arg10-kallidin; des-Arg9-bradykinin; inflammatory diseases; kallidin; kallikrein-kinin system; kininogen; kinins; plasma kallikrein; tissue kallikrein.