Potent, long-acting, orally-active bradykinin antagonists for a wide range of applications.
Actions of bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg; BK) are mediated by constitutively expressed B2 receptors, that require the full BK peptide chain, and by B1 receptors, induced in inflammation, that use BK(1-8) as ligand. In addition to many physiological and pathophysiological functions, the growth factor activity of BK evidently allows it to act as an autocrine stimulant for small cell lung cancer. A new group of BK antagonists containing the novel amino acid a-(2-indanyl)glycine provides extremely potent broad-spectrum as well as selective antagonists for all these functions.
Stewart
J M
JM
Department of Biochemistry, University of Colorado Medical School, Denver 80262, USA. john.stewart@uchsc.edu
Gera
L
L
Chan
D C
DC
Whalley
E T
ET
Hanson
W L
WL
Zuzack
J S
JS
D001920:Bradykinin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D065168:Bradykinin Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin