Sacubitril sodium | CAS#149690-05-1 | 149709-62-6 | 936623-90-4

MedKoo Cat#: 329600 | Name: Sacubitril sodium

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Sacubitril, also known as AHU377, is angiotensin receptor neprilysin inhibitor being studied for use in combination with valsartan for heart failure. Sacubitril is a prodrug that is activated to LBQ657 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.

Chemical Structure

Sacubitril sodium

CAS#149690-05-1 (sodium)

Theoretical Analysis

MedKoo Cat#: 329600

Name: Sacubitril sodium

CAS#: 149690-05-1 (sodium)

Chemical Formula: C24H28NNaO5

Exact Mass: 0.0000

Molecular Weight: 433.48

Elemental Analysis: C, 66.50; H, 6.51; N, 3.23; Na, 5.30; O, 18.45

Price and Availability

Size	Price	Availability
100mg	USD 150.00	Ready to ship
200mg	USD 250.00	Ready to ship
500mg	USD 550.00	Ready to ship
1g	USD 950.00	Ready to ship
2g	USD 1,650.00	Ready to ship
5g	USD 3,650.00	Ready to ship

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Related CAS #

1369773-39-6 (hemi-calcium) 149709-62-6 (free acid) 149690-05-1 (sodium) 936623-90-4 (Valsarta + sacubitril) 936623-90-4 137862-53-4

Synonym

Sacubitril sodium; AHU377; AHU 377; AHU-377; LCZ696. Entresto.

IUPAC/Chemical Name

sodium 4-(((2S,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoate

InChi Key

RRTBVEJIZWGATF-JKSHRDEXSA-M

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

SMILES Code

O=C([O-])CCC(N[C@@H](C[C@@H](C)C(OCC)=O)CC1=CC=C(C2=CC=CC=C2)C=C1)=O.[Na+]

Appearance

Brown solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO or water

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#M25D03K25

View CoA: current batch, Lot#M24D05K15

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Sacubitril hemicalcium salt (AHU-377 hemicalcium salt) is a potent NEP inhibitor with an IC50 of 5 nM.

In vitro activity:

In vitro incubation studies revealed that sacubitril is hydrolyzed by the liver, but not by the intestines, kidneys, or plasma, indicating that sacubitril is selectively activated by hepatic CES1. This conclusion is further supported by the observations that sacubitril was efficiently activated by purified recombinant CES1, but not CES2. Reference: Drug Metab Dispos. 2016 Apr;44(4):554-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810765/

In vivo activity:

LCZ696 (sacubitril/valsartan) and valsartan dose dependently prolonged the survival of these animals, and the effect of LCZ696-(30 mg/kg) was significantly greater than that of valsartan-(15 mg/kg). In this study, LCZ696 and valsartan dose dependently reduced urinary protein excretion in rats with subtotal nephrectomy, and the effect of LCZ696-(30 mg/kg) was significantly greater than that of valsartan-(15 mg/kg). In addition, compared to the vehicle group, glomerular sclerosis was significantly alleviated in the LCZ696-(30 mg/kg), but not the valsartan-(15 mg/kg) groups at 8 weeks in Experiment 2. Reference: Pharmacol Res Perspect. 2017 Aug; 5(4): e00336. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684857/

Preparing Stock Solutions

The following data is based on the product molecular weight 433.48 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Burke RM, Lighthouse JK, Mickelsen DM, Small EM. Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts. Circ Heart Fail. 2019 Apr;12(4):e005565. doi: 10.1161/CIRCHEARTFAILURE.118.005565. PMID: 30998392; PMCID: PMC6530564. 2. Shi J, Wang X, Nguyen J, Wu AH, Bleske BE, Zhu HJ. Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation. Drug Metab Dispos. 2016 Apr;44(4):554-9. doi: 10.1124/dmd.115.068536. Epub 2016 Jan 27. PMID: 26817948; PMCID: PMC4810765. 3. Ushijima K, Ando H, Arakawa Y, Aizawa K, Suzuki C, Shimada K, Tsuruoka SI, Fujimura A. Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual-acting angiotensin receptor-neprilysin inhibitor. Pharmacol Res Perspect. 2017 Aug;5(4):e00336. doi: 10.1002/prp2.336. PMID: 28805977; PMCID: PMC5684857. 4. Seki T, Goto K, Kansui Y, Ohtsubo T, Matsumura K, Kitazono T. Angiotensin II Receptor-Neprilysin Inhibitor Sacubitril/Valsartan Improves Endothelial Dysfunction in Spontaneously Hypertensive Rats. J Am Heart Assoc. 2017 Oct 17;6(10):e006617. doi: 10.1161/JAHA.117.006617. PMID: 29042424; PMCID: PMC5721864.

In vitro protocol:

In vivo protocol:

1. Ushijima K, Ando H, Arakawa Y, Aizawa K, Suzuki C, Shimada K, Tsuruoka SI, Fujimura A. Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual-acting angiotensin receptor-neprilysin inhibitor. Pharmacol Res Perspect. 2017 Aug;5(4):e00336. doi: 10.1002/prp2.336. PMID: 28805977; PMCID: PMC5684857. 2. Seki T, Goto K, Kansui Y, Ohtsubo T, Matsumura K, Kitazono T. Angiotensin II Receptor-Neprilysin Inhibitor Sacubitril/Valsartan Improves Endothelial Dysfunction in Spontaneously Hypertensive Rats. J Am Heart Assoc. 2017 Oct 17;6(10):e006617. doi: 10.1161/JAHA.117.006617. PMID: 29042424; PMCID: PMC5721864.

1: Luo P, Ao W, Ren Y, Xiang D. Enhancing ventricular remodeling and cardiac function in post-acute myocardial infarction with sacubitril/valsartan. Am J Transl Res. 2024 Oct 15;16(10):5865-5879. doi: 10.62347/SHSZ3751. PMID: 39544776; PMCID: PMC11558438. 2: Ye J, Zheng W, Zhang M, Zhou B, Fu Y, Mao H. Efficacy of Sarcupyrine/valsartan in the treatment of acute myocardial infarction: a meta- analysis. Am J Transl Res. 2024 Oct 15;16(10):5749-5762. doi: 10.62347/LXNH6644. PMID: 39544765; PMCID: PMC11558430. 3: Okamura K, Matsushima M, Takamiya Y, Okuda T, Sako H, Udo A, Taniguchi K, Morisaki S, Imamura I, Urata H, Miura SI. Addition of Sacubitril/Valsartan to Mineralocorticoid Receptor Antagonist Therapy in Primary Aldosteronism: Effects on Plasma Aldosterone Concentration and Plasma Renin Activity. J Clin Med Res. 2024 Oct;16(10):509-517. doi: 10.14740/jocmr6058. Epub 2024 Oct 30. PMID: 39544326; PMCID: PMC11557503. 4: Jangid MK, Doshi GM. Cross talk on therapeutic strategies: natriuretic peptides and inhibiting neprilysin in hypertension management. Hypertens Res. 2024 Nov 14. doi: 10.1038/s41440-024-01989-w. Epub ahead of print. PMID: 39543415. 5: Murayama A. Industry marketing payments to physicians and prescription patterns for sacubitril/valsartan in the USA. Heart. 2024 Nov 14:heartjnl-2024-324453. doi: 10.1136/heartjnl-2024-324453. Epub ahead of print. PMID: 39542708. 6: Fujii M, Yamashita H, Kawase Y, Bessho R, Ishii Y. Determining optimal pretreatment in cardiac surgery: an experimental study. Gen Thorac Cardiovasc Surg. 2024 Nov 14. doi: 10.1007/s11748-024-02102-1. Epub ahead of print. PMID: 39541090. 7: Nazzal MA, Iter A, Dawabsheh AQ, Bsharat MA. Valsartan/Sacubitril induced isolated angioedema of uvula: A case report. Heliyon. 2024 Oct 16;10(21):e39423. doi: 10.1016/j.heliyon.2024.e39423. PMID: 39524712; PMCID: PMC11546446. 8: Hu F, Yan S, Lin L, Qiu X, Lin X, Wang W. Correction to: Sacubitril/valsartan attenuated myocardial inflammation, fibrosis, apoptosis and promoted autophagy in doxorubicin-induced cardiotoxicity mice via regulating the AMPKα-mTORC1 signaling pathway. Mol Cell Biochem. 2024 Nov 13. doi: 10.1007/s11010-024-05159-x. Epub ahead of print. Erratum for: Mol Cell Biochem. 2024 Sep 20. doi: 10.1007/s11010-024-05117-7. PMID: 39535632. 9: Larsen AH, Lauridsen TK, Vishram-Nielsen J, Vase H, Vraa S, Wolsk E, Barasa A, Søholm H, Køber L, Dridi NP. Aetiology and treatment of chronic heart failure with reduced left ventricular function. Ugeskr Laeger. 2024 Oct 14;186(42):V05240339. Danish. doi: 10.61409/V05240339. PMID: 39531028. 10: Zha H, Zhai X, Wang L, Yang Q, Guo Q, Chen Y, Liu J, Peng H. Transforming pediatric heart failure: Efficacy of low-dose sacubitril/valsartan. Curr Probl Cardiol. 2024 Nov 6;50(1):102926. doi: 10.1016/j.cpcardiol.2024.102926. Epub ahead of print. PMID: 39510399. 11: Shoji S, Cyr DD, Hernandez AF, Velazquez EJ, Ward JH, Williamson KM, Sarwat S, Starling RC, Desai AS, Zieroth S, Solomon SD, Mentz RJ. Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights from PARAGLIDE-HF. Am Heart J. 2024 Nov 4:S0002-8703(24)00282-5. doi: 10.1016/j.ahj.2024.10.020. Epub ahead of print. PMID: 39505123. 12: Jadhav UM, Ray S, Unni TG, Sawhney JPS, Mehta A, Guha S, Karnik RD, Desai BN, Khan A, Patel K, Prajapati JS, Shah HJ, Reddy RK, Kumar S, Dutta SK, Chakraborty S, Ahmed A, Prasad RV, Chaudhary G, Kumar A, Manjappa M, Shetty S, Raja P, Shanmugam VB. Expert Opinion on the Role of Sacubitril/Valsartan in the Management of Hypertension in India. Cardiol Ther. 2024 Nov 6. doi: 10.1007/s40119-024-00390-5. Epub ahead of print. PMID: 39503972. 13: Wang Z, McCalla Z, Lin L, Tornichio D, Agyemang Y, Bastulli JA, Zhang XS, Zhu HJ, Wang X. Impact of Genetic Polymorphisms and Drug-Drug Interactions Mediated by Carboxylesterase1 on Remimazolam Deactivation. Drug Metab Dispos. 2024 Nov 5:DMD-AR-2024-001916. doi: 10.1124/dmd.124.001916. Epub ahead of print. PMID: 39500567. 14: Doi S, Kida K, Nasu T, Ishii S, Kagiyama N, Fujimoto W, Kikuchi A, Ijichi T, Shibata T, Kanaoka K, Matsumoto S, Akashi YJ. Uptitration of Sacubitril/Valsartan and Outcomes in Patients With Heart Failure　- Insight From the REVIEW-HF Registry. Circ J. 2024 Oct 31. doi: 10.1253/circj.CJ-24-0636. Epub ahead of print. PMID: 39477485. 15: Di Pietro G, Improta R, Severino P, D'Amato A, Birtolo LI, De Filippo O, Lattanzio A, De Cristofaro R, Galardo G, D'Ascenzo F, Badagliacca R, Sardella G, Volterrani M, Fedele F, Vizza CD, Mancone M. The in-hospital administration of sacubitril/valsartan in acute myocardial infarction: A meta-analysis. ESC Heart Fail. 2024 Oct 29. doi: 10.1002/ehf2.15082. Epub ahead of print. PMID: 39473218. 16: de Lucena LA, Freitas MAA, Guida CM, Hespanhol LC, de Sousa AKC, de Sousa JCV, Maia FGS. Sacubitril-Valsartan Lowers Atrial Fibrillation Recurrence and Left Atrial Volume Post-catheter Ablation: Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs. 2024 Oct 29. doi: 10.1007/s40256-024-00691-z. Epub ahead of print. PMID: 39470948. 17: Baía Bezerra F, Rodrigues Sobreira LE, Tsuchiya Sano VK, de Oliveira Macena Lôbo A, Cavalcanti Orestes Cardoso JH, Alves Kelly F, Aquino de Moraes FC, Consolim-Colombo FM. Erratum to: Efficacy of sacubitril-valsartan vs. angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in preventing atrial fibrillation recurrence after catheter ablation: a systematic review and meta-analysis. Herz. 2024 Oct 29. doi: 10.1007/s00059-024-05283-w. Epub ahead of print. Erratum for: Herz. 2024 Sep 23. doi: 10.1007/s00059-024-05275-w. PMID: 39470778. 18: Trish E, Van Nuys K, Wu J, Desai NR. The Inflation Reduction Act and Patient Costs for Drugs to Treat Heart Failure. JAMA Netw Open. 2024 Oct 1;7(10):e2441915. doi: 10.1001/jamanetworkopen.2024.41915. PMID: 39470641; PMCID: PMC11522936. 19: Stegmann T, Parentin L, Schirmer SH, Lavall P, Hagendorff A, Laufs U, Lavall D. Angiotensin receptor-neprilysin inhibition and improved ventricular-arterial coupling in heart failure with reduced ejection fraction. Am J Physiol Heart Circ Physiol. 2024 Oct 25. doi: 10.1152/ajpheart.00410.2024. Epub ahead of print. PMID: 39453422. 20: Park CS, Park J, Bae NY, Kwak S, Choi HM, Yoon YE, Lee SP, Kim YJ, Hwang IC, Kim HK. Characteristics, Predictors, and Clinical Outcomes in Heart Failure With Reduced Ejection Fraction According to a 1-Year Left Ventricular Ejection Fraction Following Sacubitril/Valsartan Treatment. J Am Heart Assoc. 2024 Nov 5;13(21):e036763. doi: 10.1161/JAHA.124.036763. Epub 2024 Oct 25. PMID: 39450740.