Perindopril-d3 (erbumine) is a deuterated version of Perindopril (erbumine). Perindopril erbumine is an angiotensin-converting enzyme inhibitor that regulates NF-κB and STAT3 signaling, inhibits glial activation and neuroinflammation, and can be used in the study of chronic kidney disease and hypertension.

Physicochemical Properties

Molecular Formula	C23H40D3N3O5
Molecular Weight	444.62
Appearance	Typically exists as solid at room temperature
Synonyms	Perindopril-d3 tert-butylamine salt; S-9490-d3 erbumine
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, primarily as quantitative tracers during drug development. Studies involving the use of deuterium-labeled drugs in humans have shown that these compounds may have certain advantages over their non-deuterated counterparts. Deuterated drugs have attracted attention due to their potential to affect the pharmacokinetic and metabolic characteristics of drugs. Deuttetrabenazine is the first deuterated drug approved by the US Food and Drug Administration. Deuttetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials indicate that many other deuterated compounds are being evaluated for use as therapeutics in human diseases, rather than just as research tools. [1] Perindopril erbumine (1 μM, 24 h) ameliorates LPS (HY-D1056)-induced reduction in AT2R expression and gliosis in rat astrocytoma cell lines (C6) and mouse microglial cell lines (BV2) [2]. Perindopril erbumine (1 μM, 24 h) inhibits LPS (HY-D1056)-induced IκBα degradation, NF-кB nuclear translocation and STAT3 activation in rat astrocytoma cell line (C6) and mouse microglial cell line (BV2)[2]. Perindopril erbumine (1 μM, 24 h) improves the imbalance of inflammatory factor release in rat astrocytoma cell line (C6) and mouse microglial cell line (BV2) induced by LPS (HY-D1056), inhibits reactive oxygen species generation and nitrite release[2].
ln Vivo	Perindopril erbumine (0.1 mg/kg, oral administration, once a day for 5 consecutive days) has a protective effect on LPS-induced neuroinflammation in rats[2]. Perindopril erbumine (0.42 mg/kg, oral administration, once a day for 4 consecutive weeks) combined with Huangqi Danshen Decoction (4.7 g/kg, oral administration, once a day for 4 consecutive weeks) alleviates adenine(HY-B0152)-induced chronic kidney disease (CKD) in rats[3]. Perindopril erbumine (0.4-1.5 mg/kg, oral administration, once a day for 4-24 weeks) has a sustained effect on blood pressure in spontaneously hypertensive rats (SHR)[5].
References	[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. [2]. Angiotensin receptor blockade modulates NFκB and STAT3 signaling and inhibits glial activation and neuroinflammation better than angiotensin-converting enzyme inhibition [J]. Molecular neurobiology, 2016, 53: 6950-6967. [3]. Combination of perindopril erbumine and huangqi-danshen decoction protects against chronic kidney disease via sirtuin3/mitochondrial dynamics pathway [J]. Evidence-Based Complementary and Alternative Medicine, 2022, 2022. [4]. Pharmacodynamic evaluation of 4 angiotensin‐converting enzyme inhibitors in healthy adult horses [J]. Journal of veterinary internal medicine, 2013, 27(5): 1185-1192. [5]. Dose-dependent effects of perindopril on blood pressure and small-artery structure [J]. Hypertension, 1994, 23(5): 659-666.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2491 mL	11.2456 mL	22.4911 mL
	5 mM	0.4498 mL	2.2491 mL	4.4982 mL
	10 mM	0.2249 mL	1.1246 mL	2.2491 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.