化合物信息

Description

Cardiovascular Disease

Description

Perindopril Erbumine (Aceon) is a potent ACE) inhibitor with IC50 of 1.05 nM.

Targets

IC₅₀

In Vitro

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]

In Vivo

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]

Clinical Trials

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.

Features

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.

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