Bradykinin B2 Receptor

The bradykinin B2 receptor is a G protein-coupled receptor, ubiquitously and constitutively expressed in healthy tissues. Bradykinin, a physiologically and pharmacologically active peptide of the kinin group of proteins, binds to the B2 receptor resulting in increased permeability of blood vessels and release of fluid into surrounding tissue. 

Multiple scenarios can excessively increase bradykinin levels including reduction of the levels or function of the C1 esterase inhibitor (C1-INH), an inhibitor of the enzyme that produces bradykinin. Other etiologies that increase bradykinin levels include mutation of factor XIIa or as a side effect of medications such as ACE inhibitors. A selective peptidomimetic, icatibant, inhibits bradykinin from binding the B2 receptor and treats rapidly all clinical signs and symptoms of a HAE attack.

The team at Pharvaris invented and developed icatibant, now sold by Shire plc under the brand name Firazyr™. Utilizing deep knowledge of the bradykinin B2 receptor and new chemistry, Pharvaris has identified novel, orally available small molecule antagonists of bradykinin:B2 receptor binding to provide a new option for patients living with HAE and other B2 receptor-mediated conditions.