| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Angiotensin-converting enzyme (ACE), which catalyzes the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. Perindoprilat competitively binds to ACE and inhibits the enzymatic hydrolysis of angiotensin I to angiotensin II, thereby reducing ATII levels in vivo and lowering blood pressure by inhibiting the pressor effect of ATII. The ACE inhibitory potency (IC50) of perindoprilat and its stereoisomers is in the nanomolar range, with four of the 32 stereoisomers, including perindoprilat, having activities in the nanomolar range.
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| ln Vitro |
In HNSCC cells, perindoprilat (1 μM) therapy suppresses angiotensin II synthesis for 10 days [2]. Treatment with perindoprilat (40 μM, 3 days) reduced the levels of fibronectin in mesangial cells [3].
Perindoprilat specifically and competitively inhibits ACE in vitro with IC50 values in the nanomolar range. Perindopril erbumine is a pro-drug metabolised in vivo by hydrolysis of the ester group to form perindoprilat, the biologically active metabolite, a potent ACE inhibitor with IC50 of 1.05 nM. The four most active diacid stereoisomers in vitro, including perindoprilat, were studied for their in vivo activity in dogs at 1 mg/kg via the oral route. |
| ln Vivo |
In mice with acute myocardial infarction, perindopril treatment (oral gavage; 1.5 mg/kg; once daily; 7 days) improves cardiac function and decreases the number of apoptotic cardiomyocytes [4]. In mice with acute myocardial infarction, perindopril (oral gavage; 1.5 mg/kg; once daily; 7 d) treatment can decrease myocardial Bax and Bcl-2 expression levels in the infarct area [4]. Mice with acute myocardial infarction can be treated with perindopril (oral gavage; 1.5 mg/kg; once daily; 7 d) to decrease the expression of myocardial TLR4/NF-κB in the infarct area [4].
In vivo, perindoprilat exerts its antihypertensive effects through competitive inhibition of ACE, reducing the conversion of angiotensin I to angiotensin II. This leads to decreased vasoconstriction, reduced aldosterone secretion, and ultimately lower blood pressure. In dog studies, the oral absorption of the active acid esters (perindopril stereoisomers) and their activation to the active diacid (perindoprilat) depended only on the chiralities of the two ring junction carbons of the perhydroindole ring. Perindopril is a long-acting ACE inhibitor effective for 24 hours, primarily utilized in the management of high blood pressure, heart failure, or stable coronary artery disease. |
| Enzyme Assay |
In vitro enzyme assays for perindoprilat involve measuring ACE inhibitory activity using synthetic substrates such as Hippuryl-His-Leu (HHL). The enzyme and substrate are incubated with various concentrations of perindoprilat or its stereoisomers, and the reaction is stopped by acidification. The amount of hippuric acid produced is quantified by HPLC or spectrophotometry. IC50 values are determined from concentration-response curves. The four most active diacid stereoisomers in vitro were identified through these assays.
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| Cell Assay |
Cell viability assay [2]
Cell Types: HNSCC Cell Tested Concentrations: 1 μM Incubation Duration: 10 days Experimental Results: Inhibited angiotensin II production in HNSCC cells (P=0.028). Cell viability assay [3] Cell Types: Human mesangial cells Tested Concentrations: 40 μM Incubation Duration: 3 days Experimental Results: Result in MPCM-stimulated fibronectin levels diminished by 19.4±0.6% (P<0.001) and 21.7±1.0% (P< 0.001) for secreted and cell-associated fibronectin levels, respectively. Cellular assays for perindoprilat are typically conducted using cell lines expressing ACE or by measuring angiotensin II-induced responses in vascular smooth muscle cells or other relevant cell types. The compound's ability to inhibit ACE activity in cellular contexts can be assessed by measuring the conversion of exogenous angiotensin I to angiotensin II or by monitoring downstream signaling events such as intracellular calcium mobilization or MAP kinase activation. These assays confirm the potent ACE inhibitory activity of perindoprilat at the cellular level. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J mouse coronary artery ligation [4]
Doses: 1.5 mg/kg Route of Administration: po (oral gavage); 1.5 mg/kg; one time/day; 7 days Experimental Results: Compared with the acute myocardial infarction group, myocardial infarction The number of apoptotic cells was Dramatically diminished (p<0.05). Animal/Disease Models: C57BL/6J mouse coronary artery ligation [4] Doses: 1.5 mg/kg Route of Administration: po (oral gavage); 1.5 mg/kg; one time/day; 7 days Experimental Results: Bax gene in the infarct area of mice with acute myocardial infarction and diminished protein expression levels. Animal/Disease Models: C57BL/6J mouse coronary artery ligation [4] Doses: 1.5 mg/kg Route of Administration: po (oral gavage); 1.5 mg/kg; one time/day; 7 days Experimental Results: Compared with the acute myocardial infarction group, infarction The number of NF-κB p50 protein staining in the nucleus of the area diminished (p<0.05). In vivo animal studies for perindoprilat and its prodrug perindopril typically involve administration to normotensive or hypertensive rat or dog models. Blood pressure is monitored via telemetry or tail-cuff plethysmography. The oral absorption of active acid esters and their activation to the active diacid (perindoprilat) was studied in dogs at 1 mg/kg via the oral route. It was concluded that oral absorption and activation depended only on the chiralities of the two ring junction carbons of the perhydroindole ring. Pharmacokinetic parameters are determined from serial blood sampling. |
| ADME/Pharmacokinetics |
The conversion of perindopril to perindoprilat is not complete, and both the parent drug and its active metabolite have distinct pharmacokinetic profiles. Oral bioavailability of perindopril is approximately 65-95%, while perindoprilat (the active metabolite) has an oral bioavailability of approximately 20-25% of the oral perindopril dose. Time to peak plasma concentration (Tmax) is ~1 hour for perindopril and 3-8 hours for perindoprilat. Elimination half-life is ~1-2 hours for perindopril, and biphasic for perindoprilat: 3-10 hours (initial) and 30-120 hours (terminal). Approximately 20-30% of an oral dose is converted to perindoprilat.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have established the safety profile of perindoprilat and its prodrug perindopril. As a potent ACE inhibitor, perindoprilat can cause dose-dependent hypotensive effects, and toxicity is primarily related to its pharmacological activity. The compound is contraindicated in pregnancy due to the risk of fetal toxicity (ACE inhibitor fetopathy). In preclinical studies, the most common adverse effects are related to excessive ACE inhibition, including hypotension, hyperkalemia, and renal impairment. The compound has been extensively studied in clinical trials and is widely used in clinical practice.
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| References | |
| Additional Infomation |
Perindopril is a dipeptide formed by the condensation of a carboxyl group of N-[(1S)-1-carboxyethyl]-L-n-valine with the amino group of (2S,3aS,7aS)-octahydroindole-2-carboxylic acid. It is the major active metabolite of perindopril. It has multiple functions, including antihypertensive activity, EC 3.4.15.1 (peptidyl dipeptidase A) inhibition, and drug metabolite activity. It is an organic heterobicyclic compound belonging to the dipeptide, dicarboxylic acid, and L-alanine derivatives. It is the active metabolite of the prodrug [perindopril]. Perindopril is an angiotensin-converting enzyme inhibitor. The mechanism of action of perindopril is as an angiotensin-converting enzyme inhibitor. Perindopril is a non-thiol angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Perindopril inhibits ACE, thereby inhibiting the conversion of angiotensin I to angiotensin II; therefore, angiotensin II-mediated vasoconstriction and angiotensin II-stimulated aldosterone secretion from the adrenal cortex are suppressed, resulting in diuresis and sodium excretion. See also: Perindopril tert-butylamine (active ingredient).
Perindoprilat (S-9490) is the active metabolite of perindopril, a long-acting ACE inhibitor effective for 24 hours. The compound is primarily utilized in the management of high blood pressure, heart failure, or stable coronary artery disease. The conversion of the prodrug perindopril to its active metabolite perindoprilat is a hepatic process mediated primarily by the CES1 enzyme. Understanding this pathway and the distinct pharmacokinetic profiles of both compounds is fundamental for drug development, clinical pharmacology, and optimizing therapeutic strategies. Perindopril is available in various formulations and is widely prescribed globally for cardiovascular conditions. |
| Molecular Formula |
C17H28N2O5
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| Molecular Weight |
340.42
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| Exact Mass |
340.199
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| CAS # |
95153-31-4
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| PubChem CID |
72022
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
568.1±45.0 °C at 760 mmHg
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| Melting Point |
153-155ºC
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| Flash Point |
297.4±28.7 °C
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| Vapour Pressure |
0.0±3.4 mmHg at 25°C
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| Index of Refraction |
1.535
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| LogP |
2.37
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
24
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| Complexity |
495
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CCC[C@@H](C(=O)O)N[C@@H](C)C(=O)N1[C@H]2CCCC[C@H]2C[C@H]1C(=O)O
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| InChi Key |
ODAIHABQVKJNIY-PEDHHIEDSA-N
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| InChi Code |
InChI=1S/C17H28N2O5/c1-3-6-12(16(21)22)18-10(2)15(20)19-13-8-5-4-7-11(13)9-14(19)17(23)24/h10-14,18H,3-9H2,1-2H3,(H,21,22)(H,23,24)/t10-,11-,12-,13-,14-/m0/s1
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| Chemical Name |
(2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid
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| Synonyms |
Perindoprilate; Perindoprilat
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
H2O : ~250 mg/mL (~734.41 mM)
DMSO : ~125 mg/mL (~367.20 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9375 mL | 14.6877 mL | 29.3755 mL | |
| 5 mM | 0.5875 mL | 2.9375 mL | 5.8751 mL | |
| 10 mM | 0.2938 mL | 1.4688 mL | 2.9375 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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