Recent developments of cathepsin inhibitors and their selectivity

Abstract

Cathepsins play an important role in the degradation of host connective tissues, the generation of bioactive proteins and antigen processing. They have been implicated in osteoporosis, muscular dystrophy, rheumatoid arthritis, bronchitis, emphysema, viral infection, cancer metastasis and neurodegenerative diseases, such as Alzheimer’s disease and Huntington’s disease. Recently, increased interest in cathepsin inhibitors has been generated with potential therapeutic targets, such as cathepsin K or cathepsin L for osteoporosis and cathepsin S for immune modulation. Of the 53 patents assessed in this review, granted between March 1998 and February 2001, there were 40 patents related to cysteine proteinase inhibitors, 7 related to aspartic proteinase inhibitors and 6 related to serine proteinase inhibitors. Of the 40 patents, 14 disclosed the novel compounds that were more selective against cathepsin K or cathepsin S than cathepsin B and cathepsin L. The compounds, showing experimental evidences, were evaluated and their biological activities in animal models determined. However, only 4 patents presented significant results in vivo. These patents may be a basis for promoting further evaluation and developing second generation cathepsin inhibitors.

• aspartic
• cathepsin inhibitor
• cysteine proteinase inhibitor
• proteinase inhibitor
• selectivity
• serine proteinase inhibitor