ENGINEERED PROTEIN INHIBITOR OF HUMAN NEUTROPHIL ELASTASE EPI-hNE4 (DX-890) A NEW TREATMENT FOR CYSTIC FIBROSIS
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چکیده
EPI-hNE4 is a highly specific and potent (Ki=4x10 M) inhibitor of human neutrophil elastase (hNE), currently under development at Debiopharm for the treatment of cystic fibrosis (CF). It has been engineered by means of a specific technology, “Directed Evolution of Novel Binding Proteins”, invented and patented by Dyax Corporation Cambridge, U.S. It is derived from the second Kunitz-type domain of inter-α-inhibitor protein (ITI-D2) and produced by fermentation in Pichia pastoris. It contains 56 amino acids, with a molecular weight (MW) of 6,237 daltons. EPI-hNE4 is resistant to oxidative and proteolytic inactivation. Pharmacological activity
منابع مشابه
EPI-hNE4, a proteolysis-resistant inhibitor of human neutrophil elastase and potential anti-inflammatory drug for treating cystic fibrosis.
EPI-hNE4 (depelstat) is a potent inhibitor of human neutrophil elastase derived from human inter-alpha-trypsin inhibitor and designed to control the excess proteolytic activity in the sputum of cystic fibrosis patients. We analyzed its resistance to the proteolysis it is likely to encounter at inflammatory sites in vivo. EPI-hNE4 resisted hydrolysis by neutrophil matrix metalloproteases (MMPs) ...
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