Study on Lead Compounds of Cathepsin C Inhibitor

Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD) is clinical syndrome of respiratory failure with high morbidity and mortality in the worldwide. Although the pathophysiology of ALI has been made in understanding, however, there is still lack innovative and useful medicine in clinical to reduce mortality. Emerging data suggest that excessive release of human neutrophil serine proteases (NSPs) mediate tissue damage, and therefore prolonged neutrophil accumulation has an important role in the pathogenesis of many diseases. Cathepsin C is a protease that is able to modulate and activate NSPs. In addition, there is not cathepsin C inhibitor marketed now. Thus, cathepsin C inhibitor may prove to be targets for the generation of agents in the treatment of neutrophilic inflammatory disease. A previous study enabled us to identify 1,2,3,6-tetra-O-galloyl-β-D-glucose (1, also call 1236TGG) from aqueous extracts of Rhois Galla, which inhibited cathepsin C activity with an IC50 value at 32.69 ± 2.95 nM. Therefore, 1236TGG derivatives will be designed, synthesized, evaluated, and developed using rational drug design. Finally, the pharmacokinetic analysis of bioactive derivatives will also be determined herein.

Project ID:PC10907-0909
External Project ID:MOST109-2320-B182-020-MY3