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LCZ696 (LCZ-696; LCZ 696; Entresto; Sacubitril mixture with Valsartan), the combination of valsartan with sacubitril in 1:1 molar ratio, is an orally bioavailable and dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) approved in 2015 for the treatment of hypertension and heart failure.
Physicochemical Properties
| Molecular Formula | C48H55N6NA3O8.2.5H2O |
| Molecular Weight | 956.99 |
| CAS # | 936623-90-4 |
| Related CAS # | Valsartan;137862-53-4;Valsartan-d9;1089736-73-1; Sacubitril;149709-62-6;Sacubitril-d4 hemicalcium salt;Sacubitril-13C4 hemicalcium salt;Sacubitril sodium;149690-05-1;Sacubitril-d4;1884269-07-1; 369773-39-6 (hemi-calcium) ; 936623-90-4; 149690-05-1 (sodium); 936623-90-4 (Valsarta + sacubitril) ; 137862-53-4 |
| Appearance | White to light yellow solid |
| LogP | 5.347 |
| SMILES | C(C1C=CC(C2=CC=CC=C2C2=NN=NN2)=CC=1)N(C(=O)CCCC)[C@H](C(=O)O)C(C)C.C(C1C=CC(C2C=CC=CC=2)=CC=1)[C@@H](NC(=O)CCC(=O)O)C[C@@H](C)C(=O)OCC.[NaH].O |
| InChi Key | UOLUPHRXIRFONO-JOYYXRJNSA-K |
| InChi Code | InChI=1S/C24H29N5O3.C24H29NO5.3Na.H2O/c1-4-5-10-21(30)29(22(16(2)3)24(31)32)15-17-11-13-18(14-12-17)19-8-6-7-9-20(19)23-25-27-28-26-23;1-3-30-24(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;;;;/h6-9,11-14,16,22H,4-5,10,15H2,1-3H3,(H2,25,26,27,28,31,32);4-12,17,21H,3,13-16H2,1-2H3,(H,25,26)(H,27,28);;;;1H2/q;;3*+1;/p-3/t22-;17-,21+;;;;/m01..../s1 |
| Chemical Name | sodium (S)-5-(4-((N-(1-carboxylato-2-methylpropyl)pentanamido)methyl)-[1,1-biphenyl]-2-yl)tetrazol-1-ide 4-(((2S,4R)-1-([1,1-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoate hydrate |
| Synonyms | valsartan / sacubitril (1:1); LCZ-696; LCZ696; LCZ 696; trade name: Entresto. |
| 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 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) |
Biological Activity
| Targets | Angiotensin receptor & neprilysin |
| ln Vitro | In an experimental model of diabetic cardiomyopathy (DCM), sacubitril/valsartan (LCZ696; 1-30 µM; 0.5 hours) reduces the apoptotic process of HG-treated H9C2 cells[4]. The ratio of Bax/Bcl-2 and the expression level of cleaved caspase-3 are increased in HG-treated H9C2 cells by sacubitril/Valsartan (1-30 µM; 0.5 hours)[4]. |
| ln Vivo | Sacubitril/Valsartan (LCZ696; administered intraperitoneally at a dose of 68 mg/kg for a duration of 4 weeks) considerably diminishes interstitial fibrosis in both the noninfarct and peri-infarct zones[2]. |
| Cell Assay |
Apoptosis Analysis[4] Cell Types: HG-treated H9C2 cells Tested Concentrations: 1, 10, or 30 µM Incubation Duration: 0.5 hrs (hours) Experimental Results: Inhibited HG-treated H9C2 cells apoptosis. Western Blot Analysis[4] Cell Types: HG-treated H9C2 cells Tested Concentrations: 1, 10, or 30 µM Incubation Duration: 0.5 hrs (hours) Experimental Results: Increased the expression level of cleaved caspase- 3 and the ratio of Bax/Bcl-2. |
| Animal Protocol |
Animal/Disease Models: Adult 6- to 8weeks old male SD (Sprague-Dawley) rats (220-250 g body weight) [2] Doses: 68 mg/kg Route of Administration: Perpo (oral gavage) for 4 weeks Experimental Results: demonstrated small weights and decreased interstitial fibrosis both in the noninfarct zone and peri-infarct zone. |
| References |
[1]. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010 Apr;50(4):401-14. [2]. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circ Heart Fail. 2015 Jan;8(1):71-8. [3]. Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells. PLoS One. 2016 May 12;11(5):e0154605. [4]. Feature article: LCZ696, an angiotensin receptor-neprilysin inhibitor, ameliorates diabeticcardiomyopathy by inhibiting inflammation, oxidative stress and apoptosis. Exp Biol Med (Maywood). 2019 Sep;244(12):1028-1039. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.61 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (2.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (104.39 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0449 mL | 5.2247 mL | 10.4494 mL | |
| 5 mM | 0.2090 mL | 1.0449 mL | 2.0899 mL | |
| 10 mM | 0.1045 mL | 0.5225 mL | 1.0449 mL |