LCZ696 | Valsartan | sacubitril | CAS#936623-90-4 | ARNi inhibitior

LCZ696 (Valsarta + sacubitril)
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 314266

CAS#: 936623-90-4 (Valsarta + sacubitril)

Description: LCZ696 is a potent ARNi inhibitor and an investigational drug to treat heart failure. Chemically, LCZ696 is a mixture of valsartan and sacubitril in a 1:1 molar ratio. As of 2014 it is being developed by Novartis. LCZ696 is co-crystallized valsartan and sacubitril, in a one-to-one molar ratio. According to Sci-Finder database, LCZ696 has a formula as (valsartan)(sacubitril)(3Sodium)(5/2 hydrate), or (2 valsartan)(2 sacubitril) (6 Sodium)(5 hydrate), which has results C96H120N12Na6O21. Molecular Weight: 1915.99 . However, according to wikipedia, One LCZ696 complex consists of 6 valsartan anions, 6 sacubitril anions, 18 sodium cations, and 15 molecules of water, resulting in the molecular formula C288H330N36Na18O48·15H2O and a molecular mass of 5748.03 g/mol. The substance is a white powder consisting of thin hexagonal plates. It is stable in solid form as well as in aqueous (watery) solution with a pH of 5 to 7, and has a melting point of about 138 °C (280 °F).(http://en.wikipedia.org/wiki/Valsartan/sacubitril)

Chemical Structure

LCZ696 (Valsarta + sacubitril)

CAS# 936623-90-4 (Valsarta + sacubitril)

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 314266
Name: LCZ696 (Valsarta + sacubitril)
CAS#: 936623-90-4 (Valsarta + sacubitril)
Chemical Formula: C96H120N12Na6O21
Exact Mass: 0.00
Molecular Weight: 1,915.990
Elemental Analysis:

Price and Availability

Size	Price	Availability
10mg	USD 90	Ready to ship
25mg	USD 150	Ready to ship
50mg	USD 250	Ready to ship
100mg	USD 450	Ready to ship
200mg	USD 750	Ready to ship
500mg	USD 1250	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

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: LCZ696; LCZ-696; LCZ 696. valsartan / sacubitril (1:1). Brand name: Entresto.

IUPAC/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

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

SMILES Code: CC(C)[C@@H](C([O-])=O)N(C(CCCC)=O)CC1=CC=C(C2=CC=CC=C2C3=NN=N[N-]3)C=C1.O=C(OCC)[C@H](C)C[C@H](NC(CCC([O-])=O)=O)CC4=CC=C(C5=CC=CC=C5)C=C4.[Na+].[Na+].[Na+].O

Appearance: 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 (100mg/mL) and water (50mg/mL)

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

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: Valsartan/sacubitril (brand name Entresto, previously known as LCZ696) is a combination drug consisting of two antihypertensives (blood pressure lowering drugs), valsartan and sacubitril, in a 1:1 mixture by molecule count developed by Novartis. The combination is often described as a dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) although the two effects are achieved by two different molecules. It was approved under the FDA's priority review process for use in heart failure on July 7, 2015.

Product Data:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#BBC50724

QC Data:

View QC data: current batch, Lot#BBC50724

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	Sacubitril/Valsartan (LCZ696), comprised of Valsartan and Sacubitril (AHU377) in 1:1 molar ratio, is a dual-acting angiotensin receptor-neprilysin (ARN) inhibitor.
In vitro activity:	By utilizing the LPS-induced HUVECs injury model, this study shows that LCZ696 has the protective capacity to suppress LPS-induced inflammation and ROS production in endothelial cells. Findings reveal that LCZ696 inhibits all the tested pro-inflammatory cytokines and chemokines’ induction, including IL-1α, TNF-β, IL-6, CXCL1, and MCP-1. These mediators are critical factors in the inflammatory processes. Currently, endothelial cells have been recognized as an important source of multifunctional cytokine production, and endothelial-derived cytokines are known to be involved in hematopoiesis, immune response, coagulation, and other processes. As a result, LCZ696 treatment significantly reduces LPS-induced intracellular ROS and MDA levels, which are lipid peroxidation products in endothelial cells. Reference: Aging (Albany NY). 2021 Apr 15; 13(7): 9582–9591. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064163/
In vivo activity:	Subsequently, it was also found that LCZ696 could inhibit cardiac hypertrophy, fibrosis and apoptosis induced by Ang II in mouse model with PAH (pregnancy-associated cardiomyopathy). Moreover, LCZ696 could inhibit the expression of ANP, βMHC and TIMP2, collagen I, collagen III and TGF-β. Ang II, a vasopressor hormone, functions in maintaining normal blood pressure and pathogenesis of cardiovascular diseases, and its overproduction forces the occurrence of hypertension in late pregnancy of mice with PAH. A previous study has demonstrated the ability of Ang II to induce high ANP and βMHC levels in cardiomyocytes in cardiac hypertrophy. TIMP2 and TIMP3 are regulators of cardiac remodeling, hypertrophy, and fibrosis in heart disease and can be induced by Ang II. Ang II was also able to induce collagen gene transcription with the involvement of the TGF-β superfamily in cardiac fibroblasts. Reference: Cell Biosci. 2019; 9: 86. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805527/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	73.3	38.27
	DMF	30.0	15.66
	Water	75.0	39.14
	Ethanol	65.0	33.93
	PBS (pH 7.2)	10.0	5.22

Preparing Stock Solutions

The following data is based on the product molecular weight 1,915.99 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. Ye S, Su L, Shan P, Ye B, Wu S, Liang G, Huang W. LCZ696 Attenuated Doxorubicin-Induced Chronic Cardiomyopathy Through the TLR2-MyD88 Complex Formation. Front Cell Dev Biol. 2021 Apr 13;9:654051. doi: 10.3389/fcell.2021.654051. PMID: 33928085; PMCID: PMC8076895. 2. Gao A, Wang Y, Gao X, Tian W. LCZ696 ameliorates lipopolysaccharide-induced endothelial injury. Aging (Albany NY). 2021 Apr 11;13(7):9582-9591. doi: 10.18632/aging.202692. Epub 2021 Apr 11. PMID: 33839697; PMCID: PMC8064163. 3. Wang Y, Guo Z, Gao Y, Liang P, Shan Y, He J. Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy. Cell Biosci. 2019 Oct 21;9:86. doi: 10.1186/s13578-019-0348-1. Erratum in: Cell Biosci. 2020 May 4;10:61. PMID: 31649814; PMCID: PMC6805527. 4. Ge Q, Zhao L, Ren XM, Ye P, Hu ZY. LCZ696, an angiotensin receptor-neprilysin inhibitor, ameliorates diabetic cardiomyopathy by inhibiting inflammation, oxidative stress and apoptosis. Exp Biol Med (Maywood). 2019 Sep;244(12):1028-1039. doi: 10.1177/1535370219861283. Epub 2019 Jul 1. PMID: 31262190; PMCID: PMC6879777.
In vitro protocol:	1. Ye S, Su L, Shan P, Ye B, Wu S, Liang G, Huang W. LCZ696 Attenuated Doxorubicin-Induced Chronic Cardiomyopathy Through the TLR2-MyD88 Complex Formation. Front Cell Dev Biol. 2021 Apr 13;9:654051. doi: 10.3389/fcell.2021.654051. PMID: 33928085; PMCID: PMC8076895. 2. Gao A, Wang Y, Gao X, Tian W. LCZ696 ameliorates lipopolysaccharide-induced endothelial injury. Aging (Albany NY). 2021 Apr 11;13(7):9582-9591. doi: 10.18632/aging.202692. Epub 2021 Apr 11. PMID: 33839697; PMCID: PMC8064163.
In vivo protocol:	1. Wang Y, Guo Z, Gao Y, Liang P, Shan Y, He J. Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy. Cell Biosci. 2019 Oct 21;9:86. doi: 10.1186/s13578-019-0348-1. Erratum in: Cell Biosci. 2020 May 4;10:61. PMID: 31649814; PMCID: PMC6805527. 2. Ge Q, Zhao L, Ren XM, Ye P, Hu ZY. LCZ696, an angiotensin receptor-neprilysin inhibitor, ameliorates diabetic cardiomyopathy by inhibiting inflammation, oxidative stress and apoptosis. Exp Biol Med (Maywood). 2019 Sep;244(12):1028-1039. doi: 10.1177/1535370219861283. Epub 2019 Jul 1. PMID: 31262190; PMCID: PMC6879777.

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1: Fabris E, Merlo M, Rapezzi C, Ferrari R, Metra M, Frigerio M, Sinagra G. Sacubitril/Valsartan: Updates and Clinical Evidence for a Disease-Modifying Approach. Drugs. 2019 Sep;79(14):1543-1556. doi: 10.1007/s40265-019-01181-2. Review. PubMed PMID: 31432436.

2: Dewan P, Docherty KF, McMurray JJV. Sacubitril/Valsartan in Asian Patients with Heart Failure with Reduced Ejection Fraction. Korean Circ J. 2019 Jun;49(6):469-484. doi: 10.4070/kcj.2019.0136. Review. PubMed PMID: 31172710; PubMed Central PMCID: PMC6554586.

3: De Vecchis R, Ariano C. Vasodilatory Properties of Sacubitril/Valsartan Explored in Hypertensives Aged Over 55 Years: A Meta-Analysis. High Blood Press Cardiovasc Prev. 2019 Apr 1. doi: 10.1007/s40292-019-00313-9. [Epub ahead of print] Review. PubMed PMID: 30937854.

4: Fonseca C, Brito D, Ferreira J, Franco F, Morais J, Silva Cardoso J; Experts opinion, endorsed by the Working Group on Heart Failure of the Portuguese Society of cardiology. Sacubitril/valsartan: A practical guide. Rev Port Cardiol. 2019 May;38(5):309-313. doi: 10.1016/j.repc.2018.10.008. Epub 2019 Jan 22. Review. English, Portuguese. PubMed PMID: 30679005.

5: Sauer AJ, Cole R, Jensen BC, Pal J, Sharma N, Yehya A, Vader J. Practical guidance on the use of sacubitril/valsartan for heart failure. Heart Fail Rev. 2019 Mar;24(2):167-176. doi: 10.1007/s10741-018-9757-1. Review. PubMed PMID: 30565021; PubMed Central PMCID: PMC6394573.

6: Gori M, D'Elia E, Senni M. Sacubitril/valsartan therapeutic strategy in HFpEF: Clinical insights and perspectives. Int J Cardiol. 2019 Apr 15;281:158-165. doi: 10.1016/j.ijcard.2018.06.060. Epub 2018 Nov 9. Review. PubMed PMID: 30420146.

7: Huet F, Akodad M, Kalmanovitch E, Adda J, Agullo A, Batistella P, Roubille C, Roubille F. Potential Uses of Sacubitril/Valsartan: Need for Data on Efficacy and Safety. Am J Cardiovasc Drugs. 2019 Feb;19(1):1-10. doi: 10.1007/s40256-018-0306-z. Review. PubMed PMID: 30345485.

8: Baliga RR. Sacubitril/Valsartan: The Newest Neurohormonal Blocker for Guideline-Directed Medical Therapy for Heart Failure. Heart Fail Clin. 2018 Oct;14(4):479-491. doi: 10.1016/j.hfc.2018.06.012. Epub 2018 Aug 17. Review. PubMed PMID: 30266357.

9: Dargad RR, Prajapati MR, Dargad RR, Parekh JD. Sacubitril/valsartan: A novel angiotensin receptor-neprilysin inhibitor. Indian Heart J. 2018 Jul;70 Suppl 1:S102-S110. doi: 10.1016/j.ihj.2018.01.002. Epub 2018 Jan 8. Review. PubMed PMID: 30122239; PubMed Central PMCID: PMC6097164.

10: Anderson SL, Marrs JC. Sacubitril/valsartan: evaluation of safety and efficacy as an antihypertensive treatment. Drugs Context. 2018 Aug 6;7:212542. doi: 10.7573/dic.212542. eCollection 2018. Review. PubMed PMID: 30116284; PubMed Central PMCID: PMC6089617.

11: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500875/ PubMed PMID: 29999934.

12: Das BB, Scholl F, Vandale B, Chrisant M. Sacubitril/Valsartan: potential treatment for paediatric heart failure. Cardiol Young. 2018 Sep;28(9):1077-1081. doi: 10.1017/S1047951118001014. Epub 2018 Jul 6. Review. PubMed PMID: 29979147.

13: Nicolas D, Reed M. Sacubitril/Valsartan. 2019 Oct 17. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK507904/ PubMed PMID: 29939681.

14: Yandrapalli S, Khan MH, Rochlani Y, Aronow WS. Sacubitril/valsartan in cardiovascular disease: evidence to date and place in therapy. Ther Adv Cardiovasc Dis. 2018 Aug;12(8):217-231. doi: 10.1177/1753944718784536. Epub 2018 Jun 19. Review. PubMed PMID: 29921166; PubMed Central PMCID: PMC6041873.

15: Sciatti E, Senni M, Lombardi CM, Gori M, Metra M. Sacubitril/valsartan: from a large clinical trial to clinical practice. J Cardiovasc Med (Hagerstown). 2018 Sep;19(9):473-479. doi: 10.2459/JCM.0000000000000687. Review. PubMed PMID: 29917003.

16: Liu RC. Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan. Am J Cardiovasc Drugs. 2018 Dec;18(6):473-482. doi: 10.1007/s40256-018-0280-5. Review. PubMed PMID: 29850980; PubMed Central PMCID: PMC6267534.

17: Joly JM, Desai AS. Sacubitril/Valsartan: From Clinical Trials to Real-world Experience. Curr Treat Options Cardiovasc Med. 2018 Apr 23;20(6):45. doi: 10.1007/s11936-018-0638-7. Review. PubMed PMID: 29687191.

18: Kario K. The Sacubitril/Valsartan, a First-in-Class, Angiotensin Receptor Neprilysin Inhibitor (ARNI): Potential Uses in Hypertension, Heart Failure, and Beyond. Curr Cardiol Rep. 2018 Jan 27;20(1):5. doi: 10.1007/s11886-018-0944-4. Review. PubMed PMID: 29374807.

19: Zaid Iskandar M, Lang CC. Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients. Drugs Today (Barc). 2017 Oct;53(10):545-551. doi: 10.1358/dot.2017.53.10.2722396. Review. PubMed PMID: 29286056.

20: Institute for Quality and Efficiency in Health Care. Sacubitril / Valsartan -- Benefit Assessment According to §35a Social Code Book V [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2016 Mar 30. Available from http://www.ncbi.nlm.nih.gov/books/NBK458434/ PubMed PMID: 29144684.

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LCZ696 (Valsarta + sacubitril) featured