Icatibant Chemical Properties

Density 

1.60±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,2-8°C

solubility 

Water:100.0(Max Conc. mg/mL);76.66(Max Conc. mM)

pka

3.60±0.21(Predicted)

form 

powder

color 

white

Water Solubility 

Soluble to 1 mg/ml in water

Sequence

H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH

InChIKey

QASONHYHOCRAHL-DOMVFXHKSA-N

CAS DataBase Reference

130308-48-4

Safety Information

WGK Germany 

3

MSDS

• Language:English Provider:SigmaAldrich

Icatibant Usage And Synthesis

Description

Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin), on bradykinin- and platelet-activating factor (PAF)-induced bronchoconstriction and airway microvascular leakage in anesthetized guinea pigs. Hoe 140 is highly potent and long-acting in inhibiting BK-induced hypotensive responses in the rat. Four hours after s.c. administration of 20nmol kg-1, inhibition still amounted to 60% whereas the effect of 200nmol kg-1 of d-Arg-[Hyp2, Thi5,8, d-Phe7]BK was not significant[1-2].

History

Icatibant, developed by Germany's Jerini AG (which was acquired by Shire in 2008 and subsequently by Takeda), is a specific bradykinin B2 receptor antagonist used to treat acute episodes of hereditary angioedema. It works by inhibiting the effects of bradykinin, which is associated with localized swelling, inflammation, and pain. First approved in the European Union in 2008 under the trade name Firazyr for the treatment of acute HAE attacks in adults, it received accelerated approval from the FDA in 2011 via priority review for acute HAE attacks in patients aged 18 years and older. In 2017, the European Union further expanded its approved indications to include pediatric and adolescent HAE patients aged 2 years and above.

Uses

Icatibant is an antagonist of the human bradykinin B2 receptor (B2R), that can be used for the treatment of hereditary angioedema (HAE). Upon administration, icatibant targets and binds to B2R, thereby preventing bradykinin from binding to the B2R. This may prevent bradykinin/B2R-mediated vasodilation, the resulting increase in vascular permeability, and the swelling, inflammation, and pain associated with HAE. This may also prevent or improve pulmonary edema not associated with HAE and improve the associated decrease in blood oxygen levels.

Definition

ChEBI: Icatibant is a ten-membered synthetic oligopeptide consisting of D-Arg, Arg, Pro, Hyp, Gly, Thi, Ser, D-Tic, Oic, and Arg residues joined in sequrence. A bradykinin receptor antagonist used as its acetate salt for the treatment of acut attacks of hereditary angioedema in adult patients.

brand name

Metastat (CollaGenex).

Biological Activity

Hoe 140 is highly potent and long-acting in inhibiting BK-induced hypotensive responses in the rat. Four hours after s.c. administration of 20 nmol kg¹, inhibition still amounted to 60%, whereas the effect of 200 nmol kg¹ of d-Arg—[Hyp2, Thi5,8, d-Phe7]BK was not significant. In receptor binding studies in guinea-pig ileum preparations, Hoe 140 showed an IC50 of 1.07 × 10?9mol l¹ and a KI value of 7.98 × 10?10 mol l¹.

storage

Store at -20°C

References

[1] K. Wirth. “Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies.” British Journal of Pharmacology 102 3 (1991): 774–777.
[2] T Sakamoto. “Effect of Hoe 140, a new bradykinin receptor antagonist, on bradykinin- and platelet-activating factor-induced bronchoconstriction and airway microvascular leakage in guinea pig.” European journal of pharmacology 213 3 (1992): 367–73.
[3] Y ARAI. Effect of icatibant, a bradykinin B2 receptor antagonist, on the development of experimental ulcerative colitis in mice.[J]. Digestive Diseases and Sciences, 1999, 44 4: 845-851. DOI:10.1023/a:1026694732602.
[4] MARIE-THÉRÈSE BAWOLAK . The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N at micromolar concentrations: Off-target alterations of signaling mediated by the bradykinin B1 and angiotensin receptors[J]. European journal of pharmacology, 2006, 551 1: Pages 108-111. DOI:10.1016/j.ejphar.2006.08.077.

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