Effect of SQ29,852, a new angiotensin converting enzyme (ACE) inhibitor with a phosphonic acid group, on the activity of angiotensin converting enzyme from human kidney.
1. An in vitro experiment was carried out to compare the inhibitory effect of SQ29,852 on human renal angiotensin converting enzyme (ACE) with those of captopril, enalapril and enalaprilat. 2. SQ29,852 strongly inhibited human renal ACE; its IC50 value was 1.5 x 10(-8) M. In terms of the IC50, SQ29,852's efficacy was about 1/10 of that of captopril and 1/28 of that of enalaprilat, but it was about 14 times more potent than enalapril. 3. SQ29,852 showed no inhibitory effects on cathepsin D, urinary kallikrein, renal renin, pepsin, trypsin and chymotrypsin. Its ACE-specificity was higher than that of captopril. 4. ACE inhibition by SQ29,852 was shown to be competitive, as revealed by Lineweaver-Burk plots. The affinity of SQ29,852 to ACE was shown to be high by a Ki value of 1.2 x 10(-8) M.
Hiwada
K
K
Second Department of Internal Medicine, Ehime University School of Medicine, Japan.
Inoue
Y
Y
Kokubu
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011480:Protease Inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D009943:Organophosphorus Compounds; D011480:Protease Inhibitors; D004656:Enalapril; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; C054518:ceronapril