TMC-66, a new endothelin converting enzyme inhibitor produced by Streptomyces sp. A5008.
A new endothelin converting enzyme (ECE) inhibitor, TMC-66 was isolated from the fermentation broth of Streptomyces sp. A5008. The structure of TMC-66 was elucidated by spectroscopic analyses to be a new member of benzo[a]naphthacenequinone class of antibiotics. TMC-66 had a highly selective inhibitory activity for ECE with an IC50 value of 2.9 microM. Taxonomy of the producing strain is also described.
Asai
Y
Y
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd, Saitama, Japan.
Nonaka
N
N
Suzuki
S
S
Nishio
M
M
Takahashi
K
K
Shima
H
H
Ohmori
K
K
Ohnuki
T
T
Komatsubara
S
S
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005285:Fermentation; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008666:Metalloendopeptidases; D009279:Naphthacenes / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D013302:Streptomyces / Q000145:classification / Q000378:metabolism*; D014361:Trypsin Inhibitors / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009279:Naphthacenes; D011480:Protease Inhibitors; C121903:TMC 66; D014361:Trypsin Inhibitors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes