K4 Elite
K4 Elite
A synthetic decapeptide bradykinin B2 receptor antagonist built from five non-proteinogenic residues, studied in kinin signaling, vascular permeability and inflammation models.
Icatibant (HOE-140) is a synthetic decapeptide that acts as a selective, competitive antagonist at the bradykinin B2 receptor. Five of its ten residues are non-proteinogenic amino acid analogs, including hydroxyproline, thienylalanine, D-tetrahydroisoquinoline-3-carboxylic acid and octahydroindole-2-carboxylic acid [6].
Those substitutions make the peptide resistant to the metalloproteases and peptidases that rapidly degrade native bradykinin, which is why it functions as a durable pharmacological tool for blocking B2 signaling in vivo rather than only in isolated tissue [6].
It received regulatory approval for acute hereditary angioedema attacks due to C1-inhibitor deficiency, and it is the reference B2 antagonist across the kinin research literature [3][4].
Bradykinin, generated by kallikrein cleavage of kininogen, acts at the constitutively expressed B2 receptor to drive Gq/phospholipase C signaling, endothelial nitric oxide and prostacyclin production, and increased vascular permeability. Icatibant occupies that receptor competitively without activating it [6].
Off-target characterization is part of the published record: at micromolar concentrations the peptide has been reported to inhibit aminopeptidase N, indirectly altering B1 and angiotensin receptor signaling, and separate work describes it as a balanced ligand at MRGPRX2 on human skin mast cells [5][7].
In a dextran sulfate sodium colitis model, mice received icatibant at 50 mg/kg by oral administration. Investigators reported suppression of large-intestine shortening and reduced diarrhea and general-condition scores compared with untreated colitis controls [1].
In rats given intraplantar carrageenan, researchers measured paw volume alongside tissue content of bradykinin and des-Arg9-bradykinin, and reported that icatibant reduced carrageenan-induced paw edema while captopril co-treatment altered the measured kinin profile [2].
The FAST-3 randomized, placebo-controlled trial evaluated icatibant during acute hereditary angioedema attacks, using time to onset of symptom relief as the primary endpoint and reporting a shorter median time in the icatibant arm than in the placebo arm [3].
In vitro work with human skin mast cells characterized icatibant at MRGPRX2 and described it as a balanced ligand at that receptor, which the authors relate to interpreting local injection-site reactions reported in trials [7].
Combinations examined in the research literature. Descriptive only — not a recommendation to combine compounds.