A specific chymase inhibitor, NK3201, suppresses bleomycin-induced pulmonary fibrosis in hamsters.

Abstract

We evaluated whether a chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[(3,4-dioxo-1-phenyl-7-(2-pyridyloxy))-2-heptyl]acetamide (NK3201), suppressed bleomycin-induced pulmonary fibrosis. Hamsters were orally administered NK3201 (30 mg/kg per day) or placebo, beginning 5 days before intratracheal instillation of bleomycin (10 mg/kg). Four weeks after the instillation of bleomycin, pulmonary chymase activity in placebo-treated hamsters was significantly higher than in control hamsters, whereas the activity in NK3201-treated hamsters was significantly lower than in placebo-treated hamsters. The ratio of fibrotic area to total area in NK3201-treated hamsters was significantly decreased to 54.0% of the ratio in placebo-treated hamsters. Therefore, NK3201 may be useful in the prevention of pulmonary fibrosis.

• Authors: Masato Sakaguchi, Shinji Takai, Denan Jin, Yukiko Okamoto, Michiko Muramatsu, Shokei Kim, Mizuo Miyazaki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 493 Issue 1-3 Pg. 173-6 (Jun 16 2004) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15189779 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 Elsevier B.V.

Chemical References

• Acetamides
• Collagen Type III
• Enzyme Inhibitors
• NK3201
• Pyrimidines
• RNA, Messenger
• Tissue Extracts
• Bleomycin
• Serine Endopeptidases
• Chymases

Topics

• Acetamides (administration & dosage, pharmacokinetics, therapeutic use)
• Administration, Oral
• Animals
• Bleomycin (adverse effects)
• Chymases
• Collagen Type III (drug effects, genetics)
• Cricetinae
• Drug Evaluation, Preclinical (methods)
• Enzyme Inhibitors (administration & dosage, pharmacokinetics, therapeutic use)
• Japan
• Lung (chemistry, drug effects, enzymology)
• Male
• Pulmonary Fibrosis (chemically induced, pathology, prevention & control)
• Pyrimidines (administration & dosage, pharmacokinetics, therapeutic use)
• RNA, Messenger (chemistry, drug effects, genetics)
• Serine Endopeptidases (chemistry, drug effects)
• Tissue Extracts (chemistry)