Neutrophil elastase inhibitors as treatment for COPD.

Abstract

Chronic obstructive pulmonary disease, characterised by a slowly progressive, irreversible airways limitation, is a major worldwide cause of chronic morbidity and mortality. The imbalance between human neutrophil elastase and endogenous antiproteases may cause excess human neutrophil elastase in pulmonary tissues, which may be considered a major pathogenic factor in chronic obstructive pulmonary disease. Great effort has been devoted to finding a method to restore the balance, resulting in the discovery of potent two-typed small-molecular-weight human neutrophil elastase inhibitors. In the application of chronic obstructive pulmonary disease therapy, the human neutrophil elastase inhibitors mainly focused upon include ONO-5046, MR-889, L-694,458, CE-1037, GW-311616 and TEI-8362 as the acyl-enzyme inhibitors; and ONO-6818, AE-3763, FK-706, ICI-200,880, ZD-0892 and ZD-8321 as the transition-state inhibitors. In this review, various problems that remain to be solved in the clinical use of human neutrophil elastase inhibitors are discussed.

• Authors: Hiroyuki Ohbayashi
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 11 Issue 7 Pg. 965-80 (Jul 2002) ISSN: 1354-3784 [Print] England
• PMID: 12084007 (Publication Type: Journal Article, Review)

Chemical References

• Protease Inhibitors
• Serpins
• Leukocyte Elastase

Topics

• Humans
• Leukocyte Elastase (metabolism)
• Lung (enzymology, pathology)
• Neutrophils (enzymology, pathology)
• Protease Inhibitors (metabolism)
• Pulmonary Disease, Chronic Obstructive (drug therapy, etiology, pathology)
• Serpins (therapeutic use)
• Smoking (adverse effects)