| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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| 2g |
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| 5g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Angiotensin-converting enzyme (ACE) [1]
Binding affinity for bradykinin vs. angiotensin I sites: bradykinin/angiotensin I selectivity ratio = 1.44 (vs. angiotensin I) [1] |
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| ln 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. 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. 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.
In single displacement binding assays on human umbilical vein endothelial cells (HUVECs), Perindopril Erbumine (S-9490-3) (as perindoprilat) displaced [125I]351A from ACE binding sites with an IC50 in the nanomolar range; the rank order of affinity was quinaprilat > trandolaprilat > ramiprilat > perindoprilat > enalaprilat [1]. In double displacement binding assays (with [125I]351A plus ACE inhibitor plus either bradykinin or angiotensin I at their IC50 concentrations), perindoprilat showed specific binding (B/B0) of 0.25±0.03 (47%) in the presence of bradykinin and 0.21±0.02 (33%) in the presence of angiotensin I, yielding a bradykinin/angiotensin I selectivity ratio of 1.44±0.12, which was significantly higher than that of ramiprilat, quinaprilat, trandolaprilat, and enalaprilat [1]. The natural substrates bradykinin and angiotensin I had IC50 values of 1.278 μM and 2.747 μM, respectively, indicating lower binding affinity than the ACE inhibitors [1]. |
| ln 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. 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. 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%. Administration of Perindopril Erbumine (1 mg/kg/day) significantly suppresses the hippocampal ACE activity, and prevents cognitive impairment and brain injury in rats with Alzheimers disease (AD).
In the PERTINENT substudy of the EUROPA trial, patients with stable coronary artery disease treated with Perindopril Erbumine (S-9490-3) (as perindopril, 8 mg daily) for 1 year showed a significant increase in bradykinin levels (+17%, P<0.05 vs. placebo) and a reduction in angiotensin II levels (-27%, P<0.05 vs. placebo) [1]. The increase in bradykinin was associated with upregulation of endothelial nitric oxide synthase (eNOS) protein expression by 19% and eNOS activity by 27% (P<0.05) [1]. Significant correlations were found between bradykinin levels and eNOS activity (r=0.43, P<0.05) and between bradykinin levels and eNOS protein expression (r=0.45, P<0.05) [1]. Perindopril restored bradykinin levels to within normal ranges found in healthy controls [1]. |
| Enzyme Assay |
Single displacement binding assay: Subconfluent HUVECs in 6-well plates were rinsed with 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) containing 5% fetal bovine serum. Various concentrations of ACE inhibitors (0.1-50 nM) or natural substrates (angiotensin I or bradykinin) were added, followed by a saturating amount of [125I]351A (a radiolabeled lisinopril analogue). After incubation at 37°C for 2 h, cells were washed twice with binding buffer, then extracted with 1 N NaOH, and radioactivity was counted. Non-specific binding was determined with 500 nM enalaprilat. IC50 values were interpolated from one-site competition fitting curves [1].
Double displacement binding assay: In this assay, three ligands were present simultaneously: [125I]351A, a single ACE inhibitor, and a single ACE substrate (angiotensin I or bradykinin). The ACE inhibitor and the natural substrate were each added at their respective IC50 concentrations. The measured [125I]351A radioactivity was directly proportional to the affinity of the ACE inhibitor for angiotensin I or bradykinin binding sites. Results were expressed as percentage [125I]351A binding relative to 100% binding when ACE inhibitors were absent and the natural substrate was present at its IC50. The bradykinin/angiotensin I selectivity ratio was calculated as the ratio of percentage binding in the presence of bradykinin versus angiotensin I at IC50 [1]. |
| Cell Assay |
Human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords by collagenase treatment (0.2% type I collagenase in Medium 199 with 20 mM HEPES for 15 min at 37°C). Cells were grown in gelatin-coated flasks in complete culture medium (Medium 199/RPMI-1640 1:1, 2 mM glutamine, 100 U/ml penicillin, 100 μg/ml streptomycin, 10 mM HEPES, 20% pooled human serum, 5 μg/ml Plasmonic) at 37°C in 5% CO2. Cells were characterized by von Willebrand factor immunostaining and cobblestone morphology. For binding assays, cells were subcultured in gelatin-coated 6-well plates (250,000 cells/well) for 24 h before experiments [1].
For single and double displacement binding assays, whole HUVECs were used without cell lysis. Cells were incubated with radioligand and unlabeled competitors under conditions (binding buffer without zinc and with high sodium) that prevented enzymatic activity of ACE, allowing only binding interactions [1]. |
| Animal Protocol |
Dissolved in DMSO, and diluted in saline; 1 or 2 mg/kg/day; p.o. Female BALB/c nude mice injected with SCC-VII cells
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Limited information suggests that breast milk contains only low concentrations of perindopril and its active metabolites, consistent with other drugs in the same class. The amount ingested by infants is very small and is not expected to have any adverse effects on breastfed infants. ◉ Effects on Breastfed Infants Ten infants were breastfed by mothers taking 5 to 20 mg of perindopril daily (feeding extent not specified). According to parents, all infants showed normal growth and development. ◉ Effects on Lactation and Breast Milk As of the revision date, no relevant published information was found. In the PERTINENT study, treatment with Perindopril Erbumine (S-9490-3) (as perindopril) was associated with a low rate of cough among ACE inhibitors, despite its preferential effect on the bradykinin binding site of ACE. This suggests that mediators other than bradykinin may be implicated in ACE inhibitor-induced cough [1]. Bradykinin is considered proinflammatory and cardioprotective; decreased bradykinin activity plays a major role in cardiovascular diseases such as hypertension, heart failure, and myocardial infarction. Increased bradykinin levels allow more nitric oxide production and exert significant antiapoptotic action on endothelium and myocytes [1]. ACE inhibitors are widely used in the treatment of cardiovascular and renal disease, and for secondary prevention of coronary artery disease. The beneficial effects are due to both reduction of angiotensin II (vasoconstriction, monocyte adhesion, SMC growth, PAI-1 increase, matrix degradation, oxygen free radicals, endothelial dysfunction) and increase of bradykinin (vasodilation, anti-adhesion of monocytes, increased eNOS expression, increased t-PA and fibrinolysis, antiremodeling effect, antioxidant effect, preserved endothelial function) [1]. |
| References |
Eur J Pharmacol.2007 Dec 22;577(1-3):1-6;J Biol Chem.2009 Nov 13;284(46):31914-20.
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| Additional Infomation |
Perindopril tert-butylamine is an adduct. It is an antihypertensive drug and an EC 3.4.15.1 (peptidyl dipeptidase A) inhibitor. It contains the perindopril (1-) domain. Perindopril tert-butylamine is the tert-butylamine salt of perindopril, an ethyl ester of a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Upon hydrolysis, perindopril tert-butylamine is converted to its active form, perindoprilat, which inhibits ACE and the conversion of angiotensin I to angiotensin II; therefore, angiotensin II-mediated vasoconstriction and angiotensin II-stimulated adrenal cortex aldosterone secretion are inhibited, leading to diuresis and sodium excretion. An angiotensin-converting enzyme inhibitor. It is used to treat patients with hypertension and heart failure. See also: perindopril (containing the active ingredient); perindoprilat (containing the active ingredient).
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| Molecular Formula |
C19H32N2O5.C4H11N
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| Molecular Weight |
441.6
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| Exact Mass |
441.32
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| CAS # |
107133-36-8
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| Related CAS # |
Perindopril;82834-16-0
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| PubChem CID |
441313
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| Appearance |
White to off-white solid powder
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| Density |
1.15 g/cm3
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| Boiling Point |
537.4ºC at 760mmHg
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| Melting Point |
126-128ºC
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| Flash Point |
278.8ºC
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| LogP |
3.713
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
31
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| Complexity |
549
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CCC[C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@H]2CCCC[C@H]2C[C@H]1C(=O)O.CC(C)(C)N
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| InChi Key |
IYNMDWMQHSMDDE-MHXJNQAMSA-N
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| InChi Code |
InChI=1S/C19H32N2O5.C4H11N/c1-4-8-14(19(25)26-5-2)20-12(3)17(22)21-15-10-7-6-9-13(15)11-16(21)18(23)24;1-4(2,3)5/h12-16,20H,4-11H2,1-3H3,(H,23,24);5H2,1-3H3/t12-,13-,14-,15-,16-;/m0./s1
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| Chemical Name |
(2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid;2-methylpropan-2-amine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (226.45 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
Solubility in Formulation 2: Saline: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2645 mL | 11.3225 mL | 22.6449 mL | |
| 5 mM | 0.4529 mL | 2.2645 mL | 4.5290 mL | |
| 10 mM | 0.2264 mL | 1.1322 mL | 2.2645 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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