| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Neprilysin (NEP). Sacubitril is a prodrug that is hydrolyzed to its active metabolite, LBQ657, a potent and selective neprilysin inhibitor (IC50 = 5 nM). The deuterated form, Sacubitril-d4, acts as an internal standard for quantifying sacubitril and its metabolites in biological samples.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
Sacubitril (AHU-377) is a potent NEP inhibitor with an IC50 of 5 nM. It is a prodrug that is metabolized in vivo to its active form, LBQ657. The deuterated version, Sacubitril-d4, has the same chemical properties as the non-labeled drug, but its different mass allows it to be used as an internal standard in LC-MS/MS to improve the accuracy and precision of drug concentration measurements. |
| ln Vivo |
Sacubitril is a widely used drug for heart failure. As the prodrug component of Entresto (sacubitril/valsartan), it has been extensively studied in vivo. In animal models, it increases plasma levels of atrial natriuretic factor (ANF) and reduces blood pressure, leading to improved cardiovascular function. In humans, the drug combination has been shown to reduce the risk of cardiovascular death and hospitalization for heart failure.
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| Enzyme Assay |
Sacubitril-d4 is not typically used in non-cellular enzyme assays as an inhibitor, but rather as an analytical standard. For enzyme assays, the non-deuterated sacubitril (or its active metabolite LBQ657) is used. In these assays, recombinant NEP is incubated with a fluorogenic substrate, and the inhibitor is added to determine its IC50. The activity of NEP is measured by the increase in fluorescence upon cleavage of the substrate.
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| Cell Assay |
Sacubitril-d4 is used in cell-based assays as an internal standard for sample preparation. Cells (e.g., hepatocytes) are treated with the non-deuterated sacubitril to study its uptake, metabolism, and effects on NEP activity. The samples are then processed, and the deuterated standard is added to the lysate to accurately quantify the amount of sacubitril and its metabolites by LC-MS/MS, compensating for any loss during sample preparation.
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| Animal Protocol |
For animal studies, animals are dosed with sacubitril (or the sacubitril/valsartan combination) orally or intravenously. Blood samples are collected at various time points. A known amount of Sacubitril-d4 is spiked into each plasma sample as an internal standard. The plasma samples are then extracted and analyzed by LC-MS/MS. The ratio of the signal from the non-deuterated drug to the signal from the deuterated internal standard is used to calculate the drug concentration.
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| ADME/Pharmacokinetics |
Sacubitril-d4 has the same pharmacokinetic properties as the non-labeled drug. It is a prodrug that is rapidly hydrolyzed in vivo to its active metabolite, LBQ657, primarily by esterases. The compound has a molecular weight of 415.52 g/mol and a molecular formula of C24H25D4NO5. It is used as an internal standard for bioanalysis, not as a therapeutic entity, so its PK as a labeled compound is not typically characterized.
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| Toxicity/Toxicokinetics |
Sacubitril is a known pharmaceutical agent with a well-characterized safety profile. As a component of Entresto, its toxicology has been extensively studied in animals and humans. Common adverse events include cough, dizziness, hypotension, and hyperkalemia. The deuterated version, Sacubitril-d4, is used in very small, non-toxic amounts as an internal standard and is not administered as a therapeutic agent. Standard safety precautions for handling research chemicals should be followed.
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| References |
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| Additional Infomation |
Sacubitril-d4 is a stable isotope-labeled compound where four hydrogen atoms have been replaced with deuterium atoms. This labeling increases the mass of the molecule by 4 Da, allowing it to be distinguished from the non-labeled compound by mass spectrometry. It is an essential internal standard for the bioanalysis of sacubitril and its metabolites in support of pharmacokinetic studies. The compound is intended for research use only and is not for human consumption.
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| Molecular Formula |
C24H25D4NO5
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|---|---|
| Molecular Weight |
415.52
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| Exact Mass |
415.229
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| CAS # |
1884269-07-1
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| Related CAS # |
Sacubitril;149709-62-6;Sacubitril hemicalcium salt;1369773-39-6;Sacubitril-d4 hemicalcium salt;Sacubitril sodium;149690-05-1
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| PubChem CID |
129010205
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
656.9±55.0 °C at 760 mmHg
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| Flash Point |
351.1±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.549
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| LogP |
3.96
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
30
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| Complexity |
550
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C(OCC)[C@H](C)C[C@H](NC(=O)C(C([2H])([2H])C(=O)O)([2H])[2H])CC1=CC=C(C=C1)C1=CC=CC=C1
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| InChi Key |
PYNXFZCZUAOOQC-JCZLLWNUSA-N
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| InChi Code |
InChI=1S/C24H29NO5/c1-3-30-24(29)17(2)15-21(25-22(26)13-14-23(27)28)16-18-9-11-20(12-10-18)19-7-5-4-6-8-19/h4-12,17,21H,3,13-16H2,1-2H3,(H,25,26)(H,27,28)/t17-,21+/m1/s1/i13D2,14D2
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| Chemical Name |
2,2,3,3-tetradeuterio-4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid
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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 |
| 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 | 2.4066 mL | 12.0331 mL | 24.0662 mL | |
| 5 mM | 0.4813 mL | 2.4066 mL | 4.8132 mL | |
| 10 mM | 0.2407 mL | 1.2033 mL | 2.4066 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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