Bradykinin antagonists: present progress and future prospects

• Published in: Immunopharmacology Vol. 43; no. 2-3; pp. 155 - 161
• Main Authors: Stewart, John M, Gera, Lajos, York, Eunice J, Chan, Daniel C, Bunn, Paul
• Format: Book Review Conference Proceeding Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-09-1999; Elsevier
• Subjects: Amino Acid Sequence; Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Bradykinin; Bradykinin - antagonists & inhibitors; Bradykinin antagonists; bradykinin B2 receptors; Bradykinin receptors; Cancer; General aspects; Growth factors; Humans; Medical sciences; Molecular Sequence Data; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Peptides, orally active; Pharmacology. Drug treatments; CPN, Carboxypeptidase N, kininase I; SUIM, Suberimidyl; BK, Bradykinin; Igl, α-2-indanylglycine; Hyp, trans-4-Hydroxyproline; Bradykinin receptors; f5f, Pentafluorophenylalanine; Bradykinin antagonists; Thi, β-2-Thienylalanine; ACE, Angiotensin I converting enzyme, kininase II; Bradykinin; Oic, Octahydroindole-2-carboxylic acid; Peptides, orally active; SCLC, Small cell lung cancer; Growth factors; Tic, Tetrahydroisoquinoline-3-carboxylic acid; Cancer; Antineoplastic agent; Peptides; Oral administration; Peptidergic receptor; Inflammation; Antagonist; Review; Malignant tumor; Biological activity; Growth factor
• ISSN: 0162-3109
• DOI: 10.1016/S0162-3109(99)00102-2

Bradykinin (BK) antagonist peptides have been powerful tools for delineating roles of kinins in both normal and pathological physiology and offer promise of drug development for a variety of inflammatory conditions and cancers. At the present time, potent peptide antagonists are available that are either specific for BK B1 or B2 receptors, or are effective on both receptor classes. Non-peptide BK B2 antagonists are now being announced and are under investigation in several companies. The best peptide B1–B2 peptide antagonist is stable against all kininases, is orally available, and has a very long lifetime in vivo. Certain dimers of this antagonist, as well as several smaller molecules, are active against several cancers, both in vitro and in vivo.