An orally active chymase inhibitor, BCEAB, suppresses heart chymase activity in the hamster

We investigated the effects of a novel chymase inhibitor, BCEAB (4-[1-{[bis -(4-methyl-phenyl)methyl]-carbamoyl)-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2- yloxy]-benzoic acid). The IC50 value of BCEAB for purified human chymase wa s 5.4 nM, whereas BCEAB did not inhibit the angiotensin-converting enzyme, elastase and tryptase. In isolated dog arteries, the IC50 value of BCEAB fo r the angiotensin 1-induced contraction in the presence of 1 muM lisinopril was 2.8 muM. In the hamster, the heart chymase activities were significant ly suppressed to 42.0% and 26.9% 3 h after oral administration of 100 and 3 00 mg of BCEAB/kg of body weight, respectively. In conclusion, BCEAB is a u seful chymase inhibitor for studying the role of chymase in vivo.