Document Detail


In vitro inhibition of human renin by statine-containing tripeptide renin inhibitor (ES-1005).
MedLine Citation:
PMID:  2485069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dipeptide and tripeptide derivatives containing a statine residue were synthesized as human renin inhibitors. ES-305, bis[(1-naphthyl)methyl]acetyl-histidyl-statine-2(S)-methylbutylami de, was found to be a highly potent human renin inhibitor that is species-specific and enzyme-specific. The replacement of the methylbutylamide of ES-305 with the leucyl-lysinol (ES-1005) showed similar high potency against human renin (Ki value of 2.4 x 10(-9) M) and monkey renin (Ki value of 7.9 x 10(-9) M) as ES-305. ES-1005 competitively inhibited human renin. The compound was about one order of magnitude less potent against pig, dog, and rabbit renins. It had moderate inhibitory potencies against cathepsin D and pepsin (IC50 of cathepsin D and pepsin of 1.6 x 10(-5) and 8.0 x 10(-6) M, respectively). ES-1005, a newly synthesized tripeptide derivative containing statine, is a highly potent inhibitor of not only primate renin but also a wide variety of nonprimate renins.
Authors:
T Kokubu; K Hiwada; E Murakami; S Muneta; Y Morisawa; Y Yabe; H Koike; Y Iijima
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  10 Suppl 7     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1987  
Date Detail:
Created Date:  1991-10-01     Completed Date:  1991-10-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S88-90     Citation Subset:  IM    
Affiliation:
2nd Department of Internal Medicine, Ehime University School of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dogs
Goats
Haplorhini
Humans
Oligopeptides / pharmacology*
Protease Inhibitors
Rabbits
Rats
Renin / antagonists & inhibitors*
Swine
Chemical
Reg. No./Substance:
0/Oligopeptides; 0/Protease Inhibitors; 115404-79-0/ES 1005; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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