Biological and pharmacological properties of highly selective new endothelin converting enzyme inhibitor WS79089B isolated from Streptosporangium roseum No. 79089.
WS79089B a highly specific endothelin converting enzyme (ECE) inhibitor has been isolated from the fermentation broth of Streptosporangium roseum No. 79089. WS79089B showed highly selective ECE inhibition activity with IC50 value of 0.14 microM and behaved as a competitive inhibitor of ECE, with Ki values of 8.9 x 10(-8) M. The sodium salt of WS79089B (FR901533) inhibited big endothelin-1 (big ET-1) induced pressor effect in a dose dependent manner when administered to male Sprague-Dawley rats intravenously dosed 2 minutes prior to big ET-1 challenge.
Tsurumi
Y
Y
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Fujie
K
K
Nishikawa
M
M
Kiyoto
S
S
Okuhara
M
M
D000192:Actinomycetales / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000201:enzymology; D005285:Fermentation; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013754:Tetracyclines / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*
D006020:Glycopeptides; D013754:Tetracyclines; C088494:WS 79089B; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon