Freselestat (ONO-6818) is reversible, nonpeptide high affinity and selective human neutrophil elastase inhibitor, which was under development by Ono for the potential treatment of inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease and chronic obstructive pulmonary disease (COPD). Freselestat mediated neutrophil elastase inhibition, leads to the reduction of interleukin 8 production and the reduction of the complement membrane attack complex formation. Freselestat competitively inhibits neutrophil elastase in humans, rats, and hamsters, but does not inhibit other proteases such as pancreatic elastase, trypsin, proteinase 3, cathepsin G, or matrix metalloproteinases. Freselestat inhibits acute lung injury induced by neutrophil elastase in rats, minimizing lung hemorrhage, the accumulation of neutrophils in the lung and suppresses leukocyte levels in an in vivo model of COPD. Freselestat was in phase I studies for COPD in Japan and the US. However, due to abnormal variations in liver function, the development of Freselestat was terminated.