Discovery and therapeutic potential of kinin receptor antagonists.

Introduction: Kinins are bioactive peptide hormones that exert biological effects by activating two types of G protein-coupled receptors namely, B(1) (B(1)R) and B(2) (B(2)R). These modulate normal physiological cellular functions, inflammatory disorders and carcinogenesis. New and novel kinin receptor antagonists have been synthesized and their efficacy evaluated.

Areas Covered: The authors provide a comprehensive review on the cellular and molecular biology of kinins and their receptors is delineated along with evolution and discovery of selective peptide and non-peptide antagonists. The authors describe the in vitro and in vivo methods used to understand the relative functional roles of B(1)R and B(2)R in physiology and pathohysiology. Furthermore, the authors translate the evaluation of kinin antagonists in selected preclinical models and associated clinical indications. Literature was surveyed from original publications, standard sources, SciFinder, patent applications and clinical trials.

Expert Opinion: The authors suggest that several key areas of functional biology need consideration, namely: re-evaluation, particularly in vivo, of the mechanism of action and relative functional roles of the B(1)R and B(2)R in physiology and acute and chronic disease in animals and man; need for improved animal models with increased use of humanized and human systems; development of fluorescent probes for use in vivo in animals and man using advanced imaging techniques; combination of kinin receptor antagonists and traditional chemotherapy for various cancers.