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Research Area
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Description
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Cardiovascular Disease |
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Biological Activity
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Description
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Perindopril Erbumine (Aceon) is a potent ACE) inhibitor with IC50 of 1.05 nM. |
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Targets
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ACE |
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IC50 |
1.05 nM [1] |
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In Vitro
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Perindopril Erbumine displays a higher binding affinity for the bradykinin binding sites than the angiotensin I binding sites of the angiotensin-converting enzyme (ACE) with bradykinin/angiotensin I selectivity ratio of 1.44. [1] Perindopril Erbumine inhibits the angiotensin- and Aβ42-to-Aβ40-converting activity of mutated ACE containing two active domains (F-ACE) with IC50 of 0.03-0.1 μM, and 0.01-0.03 μM, respectively. [2] Perindopril Erbumine (~2 μM) displays no significant cytotoxicity towards SCC-VII and KB cells, but can significantly reduce the production of angiotensin II and the transcription of VEGF in KB cells in a concentration-dependent manner. [3] |
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In Vivo
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Oral administration of Perindopril Erbumine at 2 mg/kg/day has a significant inhibitory effect on SCC-VII tumor growth, and reduces blood vessel formation surrounding the tumors in vivo due to the suppression of VEGF-induced angiogenesis. [3] Administration of Perindopril Erbumine at 2 mg/kg/day displays a strong inhibitory effect of the BNL-HCC tumor growth in rats similar to that of 20 mg/kg/day and in contrast to the AT1-R antagonist candesartan or losartan which at the dose of 20 mg/kg/day has no inhibitory effect. [4] Administration of Perindopril Erbumine at 3 mg/kg/day significantly inhibits LPS-induced apoptosis by 6.4% in RAECs in vivo than that of ramipril by 3.2%. [5] Administration of Perindopril Erbumine (1 mg/kg/day) significantly suppresses the hippocampal ACE activity, and prevents cognitive impairment and brain injury in rats with Alzheimer’s disease (AD). [6] |
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Clinical Trials
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A Phase III study to evaluate the efficacy and safety of a fixed-dose combination of Perindopril Arginine plus Amlodipine Besylate versus Perindopril Erbumine and Amlodipine Besylate in subjects with essential hypertension is currently recruiting participants. |
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Features
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Protocol
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Kinase Assay
[1]
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| ACE inhibitor binding assay |
The binding assay is based on the competitive displacement of [125I]351A by Perindopril Erbumine and performed on whole endothelial cells. Subconfluent HUVECs in 6-well plates are rinsed with 2 mL binding buffer (140 mM NaCl, 2.7 mM KCl, 1.8 mM CaCl2, 1.03 mM MgCl2, 0.42 mM NaH2PO4, 10 mM HEPES, 2 mM sodium pyruvate, 5 mM glucose, pH 7.4), and the culture medium is replaced with 2.5 mL fresh binding buffer containing 5% fetal bovine serum (FBS). A set concentration of Perindopril Erbumine (2.5–12.5 μL, 0.1–50 nM) is added to the binding buffer. A saturating amount of [125I]351A (10 μL, typically 106 cpm) is then added to each sample and the plates are incubated at 37 °C for 2 hours in a thermostatic bath. The cells are then rinsed twice with 1.5 mL binding buffer. Finally, the cells are extracted with 0.5 mL NaOH 1 N, incubated for 5 minutes, and the radioactivity is counted with a gamma counter. The radioactivity, which is due to [125I]351A binding, is inversely related to Perindopril Erbumine's affinity for endothelial ACE. The concentration of Perindopril Erbumine that displaces 50% of the bound radioligand is calculated from the competition curve. |
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Animal Study
[3]
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| Animal Models |
Female BALB/c nude mice injected with SCC-VII cells |
| Formulation |
Dissolved in DMSO, and diluted in saline |
| Doses |
1 or 2 mg/kg/day |
| Administration |
Orally |
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References |
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[1] Ceconi C, et al. Eur J Pharmacol, 2007, 577(1-3), 1-6.
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[2] Zou K, et al. J Biol Chem, 2009, 284(46), 31914-31920.
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[3] Yasumatsu R, et al. J Cancer Res Clin Oncol, 2004, 130(10), 567-573.
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[4] Yoshiji H, et al. Clin Cancer Res, 2001, 7(4), 1073-1078.
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[5] Ceconi C, et al. Cardiovasc Drugs Ther, 2007, 21(6), 423-429.
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[6] Dong YF, et al. FASEB J, 2011, 25(9), 2911-2920.
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