| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| 5g |
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| Other Sizes |
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Purity: ≥98%
Sacubitril sodium (also known as AHU-377), the sodium salt of Sacubitril,is an NEP (neutral endopeptidase 24.11)inhibitor (IC50 = 5 nM) used as a component of the heart failure medicine LCZ696 (LCZ-696; LCZ 696; Entresto; Sacubitril mixture with Valsartan). As a prodrug, Sacubitril has tobe activated to LBQ-657 by de-ethylation via esterases. LBQ657 inhibits the enzyme neprilysin, which is responsible for the degradation of atrial and brain natriuretic peptide, two blood pressure lowering peptides that work mainly by reducing blood volume.
| Targets |
NEP (neprilysin) (IC50 = 5 nM)
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|---|---|
| ln Vitro |
Brain natriuretic peptide-degrading peptides, including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and natriuretic peptide (NP), are more abundant when sacubitril is present [2].
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| ln Vivo |
Sacubitril (3, 10, and 30 mg/kg, p.o.) pretreatment raised ANP-induced plasma cGMP levels in normotensive rats by 2.4, 3.3, and 4.0 times, respectively (as compared to vehicle, 4 hours AUC) [1]. In Dahl-SS rats, sacubitril sodium (30 and 100 mg/kg, PO) has dose-dependent antihypertensive effects [1].
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| Enzyme Assay |
The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF. The synergism from these drugs arises from the vasodilating effects of valsartan through its blockade of Ang II type 1 receptor and the action of natriuretic peptides atrial natriuretic peptide and B-type natriuretic peptide (BNP) by preventing their catabolism with neprilysin resulting in increase of cyclic guanosine monophosphate. This action of neprilysin is associated with increased natriuresis, diuresis, and systemic vasodilation, since these peptides have been shown to have potent diuretic, natriuretic, and vasodilating effects. In addition, it reduces the levels of N terminal pro-BNP. Therefore, administration of LCZ-696 results in significant reduction of wall stress from pressure and volume overload of the left ventricle as demonstrated by the reduction of N terminal pro-BNP, both significant constituents of hypertension and HF, and it is safe, well tolerated and is almost free of cough and angioedema [3].
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| Animal Protocol |
We determined the relationship between atrial natriuretic peptide (ANP) and blood pressure in anesthetized, normotensive rats. We studied the relationship between NEP inhibition and elevation of plasma cGMP evoked by ANP in the absence and presence of AHU-377, an ester prodrug of LBQ657 and a component of LCZ696. Finally, using telemetry, we assessed the antihypertensive effects of AHU-377 in conscious Dahl-SS and DOCA-salt models of hypertension [1].
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| References | |
| Additional Infomation |
LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF. The synergism from these drugs arises from the vasodilating effects of valsartan through its blockade of Ang II type 1 receptor and the action of natriuretic peptides atrial natriuretic peptide and B-type natriuretic peptide (BNP) by preventing their catabolism with neprilysin resulting in increase of cyclic guanosine monophosphate. This action of neprilysin is associated with increased natriuresis, diuresis, and systemic vasodilation, since these peptides have been shown to have potent diuretic, natriuretic, and vasodilating effects. In addition, it reduces the levels of N terminal pro-BNP. Therefore, administration of LCZ-696 results in significant reduction of wall stress from pressure and volume overload of the left ventricle as demonstrated by the reduction of N terminal pro-BNP, both significant constituents of hypertension and HF, and it is safe, well tolerated and is almost free of cough and angioedema[3].
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| Molecular Formula |
C24H28NNAO5
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|---|---|
| Molecular Weight |
433.472598075867
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| Exact Mass |
433.187
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| Elemental Analysis |
C, 66.50; H, 6.51; N, 3.23; Na, 5.30; O, 18.45
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| CAS # |
149690-05-1
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| Related CAS # |
Sacubitril;149709-62-6;Sacubitril hemicalcium salt;1369773-39-6;Sacubitril-d4 hemicalcium salt;Sacubitril-d4;1884269-07-1; 149690-05-1 (sodium) 936623-90-4 (Valsarta + sacubitril); 936623-90-4 ; 137862-53-4
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| PubChem CID |
23707568
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| Appearance |
Brown solid
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| LogP |
4.547
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
31
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| Complexity |
556
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| Defined Atom Stereocenter Count |
2
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| SMILES |
[Na+].O(CC)C([C@H](C)C[C@@H](CC1C=CC(C2C=CC=CC=2)=CC=1)NC(CCC(=O)[O-])=O)=O
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| InChi Key |
RRTBVEJIZWGATF-JKSHRDEXSA-M
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| InChi Code |
InChI=1S/C24H29NO5.Na/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);/q;+1/p-1/t17-,21+;/m1./s1
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| Chemical Name |
sodium 4-(((2S,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoate
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| Synonyms |
AHU377; LCZ696; AHU 377; AHU-377; Entresto.
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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) |
DMSO: >10 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 | 2.3070 mL | 11.5348 mL | 23.0696 mL | |
| 5 mM | 0.4614 mL | 2.3070 mL | 4.6139 mL | |
| 10 mM | 0.2307 mL | 1.1535 mL | 2.3070 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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