New bradykinin antagonists having very high potency at B1 receptors

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Cited by (29)

  • Preclinical pharmacology, metabolic stability, pharmacokinetics and toxicology of the peptidic kinin B1 receptor antagonist R-954

    2014, Peptides
    Citation Excerpt :

    This may be explained by the facts that R-954 shows good in vitro/in vivo metabolic stability (Figs. 2 and 3) and albumin binding capability (Table 4), two important determinants for extending the presence and activity of molecules in vivo. Other potent peptidic B1R antagonists have been described but demonstrate either incomplete stability (e.g., R-715, B-9858, and B-9958) [20,21,35] or non-selectivity meaning that they also blocked the B2R (e.g., [desArg9]HOE140, B9858, B9430) [20,21,24,43,46,50]. Thus, R-954 stands out as perhaps the most potent, biostable, selective and specific B1R antagonist of peptide nature, available at present (see Tables 2 and 3, Fig. 2).

  • Structural modification of the highly potent peptide bradykinin B1 receptor antagonist B9958

    2008, International Immunopharmacology
    Citation Excerpt :

    The first full-chain bradykinin antagonist which showed high affinity at both B1 and B2 receptors, B9430 (DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg, Hyp, trans-4-hydroxyproline; Oic, octahydroindole-2-carboxylic acid), was developed by Gera at the Stewart laboratory a decade ago with the introduction of α-(2-indanyl)glycine (Igl) [3]. As expected, the des-Arg9-analog of B9430, B9858 (Lys-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic) and B9958 (Lys-Lys-Arg-Pro-Hyp-Gly-CpG-Ser-DTic-CpG, Tic, tetrahydroisoquinoline-3-carboxylic acid) had a remarkably high B1R antagonist activity [4,5]. Interestingly, B9858 was an insurmountable B1R antagonist in the rabbit aorta contractility assay, whereas B9958 was competitive (surmountable) [5].

  • Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V<inf>1a</inf>, V<inf>1b</inf>, V<inf>2</inf> and OT receptors: research tools and potential therapeutic agents

    2008, Progress in Brain Research
    Citation Excerpt :

    We recently reported the syntheses and some preliminary pharmacological properties of bivalent ligands for the hOTR, V1a and V1b receptors (Chini et al., 2007; Chini and Manning, 2007). Suberic acid, (HOOC–(CH2)6–COOH) utilized as reported by Gera et al. (1996), served as the spacer joining Orn or Lys residues in an OT/V1a antagonist d(CH2)5[Tyr(Me)2]OVT, and two linear V1a/OT antagonists, HO–Phaa–d-Tyr(Me)–Phe–Gln–Asn–Arg–Pro–Lys–NH2, and HOPhaa–d-Tyr(Me)–Phe–Gln–Asn–Arg–Pro–Arg–Lys–NH2. The resulting suberyl-(OC–CH2)6–CO–) bivalent ligands exhibit high affinities, in the nanomolar range, for the hOTR and V1a receptors expressed in heterologous cell systems.

  • Bradykinin receptors

    2007, xPharm: The Comprehensive Pharmacology Reference
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