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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Sacubitril-d4 hemicalcium salt targets the same enzyme as its non-deuterated parent: neprilysin (NEP), a zinc-dependent metalloprotease that degrades various vasoactive peptides, including natriuretic peptides and bradykinin. The unlabeled Sacubitril is an inactive prodrug that, after in vivo esterase-catalyzed hydrolysis to its active metabolite, Sacubitrilat (LBQ657), inhibits NEP. This results in elevated levels of natriuretic peptides, leading to vasodilation and reduced blood pressure.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
Sacubitril-d4 hemicalcium salt is not biologically active in vitro; it is a tracer for quantitation. The unlabeled parent compound, Sacubitril hemicalcium salt, is a potent NEP inhibitor with an IC50 of 5 nM. It is a component of the drug combination LCZ696 (sacubitril/valsartan), which is used to treat heart failure with reduced ejection fraction (HFrEF). The biological activity is primarily attributed to its active metabolite, Sacubitrilat. |
| ln Vivo |
Sacubitril-d4 is used as an internal standard to quantify Sacubitril and its active metabolite, Sacubitrilat, in plasma and tissues. The unlabeled parent compound, Sacubitril hemicalcium salt, is clinically used as part of the combination drug LCZ696 (Entresto®) for the treatment of heart failure. In vivo, it is rapidly converted to its active metabolite, LBQ657, which inhibits neprilysin, reducing cardiovascular risk and improving survival in HF patients.
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| Enzyme Assay |
Sacubitril-d4 hemicalcium salt is an internal standard for LC-MS/MS. A fixed concentration (e.g., 10-100 ng/mL) of the d4 internal standard is added to biological samples (e.g., plasma, tissue homogenates). Samples are extracted (e.g., by protein precipitation or solid-phase extraction) and analyzed by LC-MS/MS. Sacubitril and its active metabolite are detected in positive ion mode using specific MRM transitions. The d4 internal standard has a mass shift of +4 Da and corrects for matrix effects and extraction recovery in the quantification of Sacubitril levels.
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| Cell Assay |
Sacubitril-d4 is not used in cell-based assays. The unlabeled parent compound, Sacubitril, is used to study the NEP inhibition pathway in cellular models. For example, HEK293 cells expressing human NEP are seeded in 96-well plates. Cells are treated with Sacubitril (1-1000 nM) in the presence of a synthetic NEP fluorogenic substrate (e.g., Mca-RPPGFSAFK(Dnp)-OH). The fluorescence (ex/em = 320/405 nm) is measured over time. The IC50 for NEP inhibition is calculated from the decrease in fluorescence signal compared to the control, demonstrating the compound's ability to inhibit the enzyme in a live cell environment.
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| Animal Protocol |
Sacubitril-d4 hemicalcium salt is used as an internal standard for PK studies of Sacubitril. A standard animal protocol: male Sprague-Dawley rats (200-250 g) are administered a single oral dose of Sacubitril hemicalcium salt (10-50 mg/kg). Blood samples are collected at multiple time points (0-24 h). Plasma is separated, and a fixed concentration of Sacubitril-d4 hemicalcium salt is added. Samples are extracted and analyzed by LC-MS/MS. Pharmacokinetic parameters for Sacubitril and its active metabolite, Sacubitrilat, are calculated using non-compartmental analysis.
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| ADME/Pharmacokinetics |
Sacubitril-d4 hemicalcium salt has a molecular formula of C24H25D4NO5·0.5Ca and a molecular weight of 435.56. The powder should be stored at -20degC in a sealed container, away from moisture. In solvent, it is stable for 6 months at -80degC or 1 month at -20degC. The compound is soluble in DMSO (≥20 mg/mL) and DMF (≥20 mg/mL), and slightly soluble in ethanol (≥5 mg/mL).
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| Toxicity/Toxicokinetics |
Sacubitril is well-tolerated in clinical settings. The most common adverse events include hypotension, hyperkalemia, cough, and dizziness. The deuterated version is used in trace amounts as an analytical standard and does not pose additional safety risks beyond standard chemical handling. The unlabeled drug has a boxed warning for the risk of angioedema (swelling of the deeper layers of the skin).
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| References |
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| Additional Infomation |
Sacubitril-d4 hemicalcium salt is a research-grade stable isotope-labeled compound and is not approved for clinical use. It is used as an internal standard for the quantification of Sacubitril, a potent NEP inhibitor used in the treatment of heart failure. This product is for research use only and not for human therapeutic applications. Store as a powder at -20degC. The hemicalcium salt form is the standard pharmaceutical form of the active ingredient.
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| Molecular Formula |
C24H25D4NO50.5CA
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| Molecular Weight |
435.56
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| Related CAS # |
Sacubitril;149709-62-6;Sacubitril hemicalcium salt;1369773-39-6;Sacubitril-13C4 hemicalcium salt;Sacubitril sodium;149690-05-1;Sacubitril-d4;1884269-07-1
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| Appearance |
White to off-white solid powder
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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. |
| 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) |
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
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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 | 2.2959 mL | 11.4795 mL | 22.9589 mL | |
| 5 mM | 0.4592 mL | 2.2959 mL | 4.5918 mL | |
| 10 mM | 0.2296 mL | 1.1479 mL | 2.2959 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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