In vitro inhibition of human renin by statine-containing tripeptide renin inhibitor (ES-1005)

• Published in: Journal of cardiovascular pharmacology Vol. 10 Suppl 7; p. S88
• Main Authors: Kokubu, T, Hiwada, K, Murakami, E, Muneta, S, Morisawa, Y, Yabe, Y, Koike, H, Iijima, Y
• Format: Journal Article
• Language: English
• Published: United States 1987
• Subjects: Animals; Dogs; Goats; Haplorhini; Humans; Oligopeptides - pharmacology; Protease Inhibitors; Rabbits; Rats; Renin - antagonists & inhibitors; Swine
• ISSN: 0160-2446
• DOI: 10.1097/00005344-198706107-00014

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.