Drug intelligence / Profile preview

H6-trC1INH(MGS)

Development stage
Preclinical
Lead developer
Canadian Blood Services
Modality
Recombinant Proteins and Enzymes
Administration
Intravenous
01

Overview

H6-trC1INH(MGS) is a recombinant, truncated, and non-glycosylated variant of the human C1 esterase inhibitor (C1INH), designed for the treatment and prophylaxis of Hereditary Angioedema (HAE). This construct lacks the first 97 amino acids of the native N-terminal domain and features three mutated N-linked glycosylation sites (N216Q, N231Q, and N330Q) within the serpin domain to simplify the protein structure and facilitate expression in eukaryotic systems like *Pichia pastoris*. It includes an N-terminal hexahistidine tag for purification. Functionally, H6-trC1INH(MGS) acts as a serine protease inhibitor (serpin), targeting plasma kallikrein (Pka) and the C1s subcomponent of the complement system to regulate vascular permeability and inflammation. Due to its reduced molecular weight (~43 kDa) and lack of glycosylation, it has a short circulatory half-life, serving as a base molecule for half-life extension strategies such as fusion to serum albumin.

Other names
hexahistidine-tagged truncated C1INH with mutated glycosylation sitestruncated C1INH(MGS)trC1INH(MGS)
02

Targets

FXIIa (Coagulation Factor XIIa)KLKB1 (Plasma kallikrein)C1S (Complement component 1s subcomponent serine protease)Factor XIaC1R (Complement component 1r subcomponent)

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