Therapeutic potential of non-peptide chymase inhibitors

Background: alpha-Chymase may have a role in the pathophysiology of certain cardiac diseases (myocardial infarction, hypertrophy, fibrosis, and heart failure), vascular diseases (atherosclerosis, proliferation), skin diseases, and many fibrotic conditions. Inhibitors of chymase may be useful in these conditions. Objectives: The aim was to briefly review the pathophysiological role of chymase, and to discuss in more detail the published literature (patent and journal) relating to non-peptide chymase inhibitors. Results: The review showed that many selective inhibitors of chymase have been patented, and some show good selectivity and potency. Some of the chymase inhibitors have been shown to be effective in animal models of heart disease, vascular disease, fibrosis, and adhesion. None of the chymase inhibitors have entered clinical trial to date. Conclusions: Of the potential clinical uses of chymase inhibitors, inhibition of fibrosis seems to be the most marked effect, and suitable for advancement. It is possible that chymase inhibitors may never become first-line treatment for any disease or condition, but they may become important adjuvant treatment for the fibrosis associated with many diseases and conditions.