Ecallantide, also known as DX-88, was approved in 2009 in the
United States for treatment of hereditary angioedema (HAE), a condition
characterized by episodic attacks of localized edema in cutaneous
and mucosal tissues. HAE results from deficiencies or disorders of C1-esterase inhibitor protein (C1-
1NH). Mutation of the gene that encodes C1-1NH causes the lack or
altered activity of the serine protease, C1-1NH. C1-1NH regulates the
kallikrein–kinin (contact activation) and complement cascade systems.
Ecallantide (DX-88) was designed to inhibit the action of
plasma kallikrein. Ecallantide is a potent and selective inhibitor of
plasma kallikrein with a Ki= 25 pM. The discovery program that
identified ecallantide used phage display technology and a library of
designed variants of the first Kunitz domain of TFPI. Ecallantide, a
60-amino acid peptide, with 3-disulfide bonds, differs from TFPI by
7-amino acids. Ecallantide has been developed as a subcutaneous
administered formulation.
