title: Chymase inhibitors.
abstract: Chymase, a chymotrypsin-like serine protease that is abundant in secretory granules from mast cells, has been identified to be a key enzyme in the local renin-angiotensin system (RAS) that generates angiotensin II (Ang II) independent of angiotensin converting enzyme (ACE). The pathophysiological significance of alternative Ang II-forming pathways in human cardiovascular disease remains controversial. Although chymase inhibitors, unlike ACE inhibitors and Ang II type 1 receptor blockers (ARBs), may only play a small role in the regulation of the systemic RAS, the possible applications of chymase inhibitors as new drugs that inhibit the local RAS to prevent cardiovascular diseases are described in animal models. In this review, we discuss the possible application of chymase inhibitors as new drugs to inhibit the RAS in mainly cardiovascular diseases.
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. eyahiro@fukuoka-u.ac.jp
authors.forename: Eiji
authors.initials: E
authors.lastname: Yahiro
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imaizumi
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Uehara
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy; D001384:Azetidines / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology; D053818:Chymases / Q000037:antagonists & inhibitors* / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008407:Mast Cells / Q000502:physiology; D010080:Oxazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C487109:2-(4-(5-fluoro-3-methylbenzo(b)thiophen-2-yl)sulfonamide-3-methanesulfonylphenyl)oxazole-4-carboxylic acid; C439760:4-(1-((bis(4-methylphenyl)methyl)carbamoyl)-3-(2-ethoxybenzyl)-4-oxoazetidine-2-yloxy)benzoic acid; D000081:Acetamides; D001384:Azetidines; D001565:Benzoates; C437945:NK3201; D010080:Oxazoles; D011743:Pyrimidines; D011799:Quinazolines; C466919:SUN-C 8257; D013449:Sulfonamides; D053818:Chymases