| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Sacubitril-d4 (LBQ-657-d4) targets the same enzyme as its non-deuterated parent, Sacubitrilat. Sacubitrilat is the active neprilysin (NEP) inhibitor and is responsible for the pharmacological activity of Sacubitril prodrugs. NEP is a zinc-dependent metalloprotease that degrades vasoactive peptides. Inhibition of NEP leads to elevated levels of natriuretic peptides, thereby inducing vasodilation, natriuresis, and improved cardiovascular outcomes.
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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 is not used for biological activity assessment; it is an analytical tracer. The unlabeled parent, Sacubitrilat, is an effective inhibitor of active neprilysin (NEP). Its in vitro activity is characterized by its IC50, which is in the low nanomolar range (e.g., IC50 of 5 nM). It is used as a standard in enzyme assays to validate NEP inhibition. Sacubitrilat is also used as a positive control in studies involving the renin-angiotensin-aldosterone system (RAAS). |
| ln Vivo |
In vivo, Sacubitrilat (LBQ657) is the pharmacologically active species that exerts its blood pressure-lowering and cardioprotective effects by inhibiting NEP. It is rapidly formed from the prodrug Sacubitril via esterase activity in the liver and intestine. The deuterated version (Sacubitril-d4) is used as an internal standard to accurately measure the concentration of this active metabolite in plasma and tissues, which is essential for pharmacokinetic/pharmacodynamic (PK/PD) modeling and bioequivalence studies.
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| Enzyme Assay |
Sacubitril-d4 is an internal standard for LC-MS/MS. A fixed concentration (e.g., 10-50 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) to remove proteins and salts. The extracted sample is analyzed by LC-MS/MS. Detection is performed in positive ion mode using specific MRM transitions (e.g., m/z 365 → 277 for Sacubitrilat). The d4 internal standard has a mass shift of +4 Da (m/z 369 → 281). The peak area ratio is used to calculate the concentration of Sacubitrilat in the sample.
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| Cell Assay |
A standard cell-based assay for the parent compound is not applicable for this active metabolite. To measure NEP activity in cell lysates, a cell-free enzyme assay is typically used. However, to confirm the formation of the active metabolite from a prodrug, cells (e.g., Caco-2 intestinal epithelial cells or primary hepatocytes) are incubated with the prodrug Sacubitril for 0-24 h. The cell culture medium is collected, and Sacubitril-d4 is added as an internal standard. The samples are analyzed by LC-MS/MS to quantify the amount of Sacubitrilat formed, which demonstrates the conversion efficiency.
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| Animal Protocol |
Sacubitril-d4 is used as an internal standard for PK studies of the active metabolite. A standard animal protocol: Male Sprague-Dawley rats (200-250 g) are administered a single oral dose of Sacubitril (10-50 mg/kg). Blood samples are collected at pre-dose and at multiple time points (0-24 h). Plasma is separated and spiked with a fixed concentration of Sacubitril-d4 internal standard. Samples are extracted and analyzed by LC-MS/MS. The plasma concentration-time curve of Sacubitrilat (LBQ657) is generated. PK parameters (Cmax, Tmax, AUC, t½) are calculated. The ratio of Sacubitrilat to Sacubitril (AUC) indicates the rate and extent of metabolic activation.
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| ADME/Pharmacokinetics |
Sacubitril-d4 has a molecular weight of 387.5 g/mol (for the free acid). It is a deuterated compound of LBQ657. The powder should be stored at -20degC for up to 3 years, sealed and away from moisture. In solvent, it is stable for 1 year at -80degC. Specific PK data for the labeled compound are not provided, but the unlabeled active metabolite has a half-life of approximately 10-12 hours in humans.
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| Toxicity/Toxicokinetics |
Sacubitrilat (LBQ657) is an active metabolite that is generally well-tolerated in patients when formed from the prodrug. Its adverse effects are similar to those of Sacubitril, including hypotension, hyperkalemia, and angioedema. The deuterated version is used in trace amounts as an analytical standard and does not pose additional safety risks beyond standard chemical handling. Standard safety precautions for handling pharmaceutical metabolites should be followed.
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| References |
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| Additional Infomation |
Sacubitril-d4 (Desethyl Sacubitril-d4; LBQ-657-d4) is a research-grade stable isotope-labeled compound. It is used as an internal standard for the quantification of the active neprilysin (NEP) inhibitor Sacubitrilat. This product is for research use only and not for human therapeutic applications. Store as a powder at -20degC. The accurate quantification of this metabolite is crucial for the development and monitoring of Sacubitril-containing drugs like Entresto®.
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| Molecular Formula |
C22H21D4NO5
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| Related CAS # |
Sacubitrilat;149709-44-4
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| Appearance |
Typically exists as solid at room temperature
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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.) |
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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