HOE-140

Description

Although it is a rare disease, HAE is an autosomal dominant disorder that can be potentially life-threatening when swelling manifests itself within the upper airways. Antagonism of the constitutively expressed B2 receptor, therefore, would not only be beneficial in the treatment of HAE but also find application in inflammatory, allergic, and hyperalgesic disorders.Designed to possess enhanced metabolic stability with the inclusion of five non-proteinogenic amino acids, icatibant is a competitive and selective B2 receptor antagonist (devoid of activity against the inducible B1 receptor) with a K_i of 2.2±0.7 nM, and it is the first downstream targeting agent to receive regulatory approval. It joins purified C1 esterase inhibitor, danazol (an attenuated androgen), and tranexamic acid (an antifibrinolytic agent) as acute and prophylactic treatments for HAE.

Originator

Jerini (Germany)

Uses

Icatibant Acetate is a bradykinin B2 receptor antagonist that has been recently approved for treatment of acute attacks of hereditary angioedema (HAE).

Uses

Antagonist (bradykinin).

Definition

ChEBI: An acetate salt obtained by combining icatibant with acetic acid. Used for the treatment of acute attacks of hereditary angioedema in adult patients.

brand name

Metastat (CollaGenex);Firazyr.

Biochem/physiol Actions

B2 bradykinin receptors are present in the sensory neurons. Activation of B2 receptor by bradykinin is associated with pro-inflammatory, pain producing and cardiovascular responses. HOE-140 is a selective B2 bradykinin receptor antagonist. Presence of HOE-140 suppresses the effects of bradykinin and has been shown to have anti-hyperalgesic response, particularly towards inflammatory pain.

Synthesis

The peptidomimetic is prepared by standard solidphase technology on Wang resin employing Fmoc chemistry. Following trifluoroacetic acid cleavage with appropriate scavengers and HPLC purification, icatibant is ultimately isolated as its acetate salt.