Current synthetic inhibitors of human neutrophil elastase in 2005

Abstract

The human neutrophil elastase (HNE)-related diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), are a serious problem worldwide. To prevent excessive production of HNE, which is a major pathogenic factor of these disorders, and to restore the appropriate balance between HNE and its inhibitors, research and development of potent synthetic HNE inhibitors has been conducted for > 30 years worldwide. At present, the following four agents can be described as the most successful: the acyl-enzyme inhibitors, ONO-5046 and MR-889, and the transition-state inhibitors, ONO-6818 and AE-3763. Additionally, protein inhibitors such as DX-890 (EPI-hNE-4), recombinant α1-antitrypsin, elafin and secretory leukocyte protease inhibitor (SLPI) are also being developed and actively researched in 2005. This review focuses upon the major synthetic HNE inhibitors, including those patented in 2004.

Keywords::

• acyl-enzyme inhibitor
• elafin
• human neutrophil elastase (HNE)
• protein inhibitor
• secretory leukocyte protease inhibitor (SLPI)
• transition-state inhibitor