Author： Ohbayashi Hiroyuki
Publisher： Informa Healthcare
ISSN： 1354-3776
Source： Expert Opinion on Therapeutic Patents, Vol.12, Iss.1, 2002-01, pp. : 65-84
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Abstract
The imbalance between human neutrophil elastase (HNE, EC 3.4.21.37) and endogenous antiproteinases is considered to cause various HNE-mediated inflammatory disorders, such as adult respiratory distress syndrome, cystic fibrosis, pulmonary emphysema and rheumatoid arthritis. To realise the optimum therapeutic approach and investigate accurate pathogenic mechanism of these diseases, new synthetic HNE inhibitors have been under development. Through the long-time intensive research by many pharmaceutical industries and institutes, the most promising strategies at present may result in the application of two-types of small-molecular-weight HNE inhibitors: acyl-enzyme inhibitors (ONO-5046, L-694458 and MR-889) or transition-state inhibitors (ONO-6818, AE-3763 and FK-706). This review mainly focuses on the experimental and clinical evaluation of recent synthetic HNE inhibitors, including 14 current patent reports claimed since 1998.
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