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 was 5.4 nM, whereas BCEAB did not inhibit the angiotensin-converting enzyme, elastase and tryptase. In isolated dog arteries, the IC50 value of BCEAB for the angiotensin I-induced contraction in the presence of 1 microM lisinopril was 2.8 microM. In the hamster, the heart chymase activities were significantly suppressed to 42.0% and 26.9% 3 h after oral administration of 100 and 300 mg of BCEAB/kg of body weight, respectively. In conclusion, BCEAB is a useful chymase inhibitor for studying the role of chymase in vivo.
Takai
S
S
Department of Pharmacology, Osaka Medical College, Takatsuki City, Japan. pha010@art.osaka-med.ac.jp
Jin
D
D
Sakaguchi
M
M
Kirimura
K
K
Miyazaki
M
M
D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D053818:Chymases; D006224:Cricetinae; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009206:Myocardium / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*
C439760:4-(1-((bis(4-methylphenyl)methyl)carbamoyl)-3-(2-ethoxybenzyl)-4-oxoazetidine-2-yloxy)benzoic acid; D001384:Azetidines; D001565:Benzoates; D011480:Protease Inhibitors; D000804:Angiotensin II; D012697:Serine Endopeptidases; D053818:Chymases