LCZ696 (Valsarta + sacubitril)
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MedKoo CAT#: 314266

CAS#: 936623-90-4

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)


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100mg
USD 150
1g
USD 1150
10g
USD 3950
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200mg
USD 250
2g
USD 1950
50g
USD 6950
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500mg
USD 650
5g
USD 2950
1kg
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LCZ696, purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order > 10g may be 2 weeks. Kilogram is available in one month.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 314266
Name: LCZ696 (Valsarta + sacubitril)
CAS#: 936623-90-4
Chemical Formula: C96H120N12Na6O21
Exact Mass:
Molecular Weight: 1915.99
Elemental Analysis:


Related CAS #: 936623-90-4   137862-53-4   149690-05-1 (sodium)  

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


Technical Data

Appearance:
Solid powder

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

Certificate of Analysis:

Safety Data Sheet (MSDS):

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).

Harmonized System Code:
2934990300


Additional Information

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.


References

1: Ito S, Satoh M, Tamaki Y, Gotou H, Charney A, Okino N, Akahori M, Zhang J. Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction. Hypertens Res. 2015 Feb 19. doi: 10.1038/hr.2015.1. [Epub ahead of print] PubMed PMID: 25693859.

2: Voors AA, Gori M, Liu LC, Claggett B, Zile MR, Pieske B, McMurray JJ, Packer M, Shi V, Lefkowitz MP, Solomon SD; for the PARAMOUNT Investigators. Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction. Eur J Heart Fail. 2015 Feb 6. doi: 10.1002/ejhf.232. [Epub ahead of print] PubMed PMID: 25657064.

3: Sabourin G. [Heart failure and LCZ696]. Perspect Infirm. 2015 Jan-Feb;12(1):61. French. PubMed PMID: 25651686.

4: Minguet J, Sutton G, Ferrero C, Gomez T, Bramlage P. LCZ696 : a new paradigm for the treatment of heart failure? Expert Opin Pharmacother. 2015 Feb;16(3):435-46. doi: 10.1517/14656566.2015.1000300. PubMed PMID: 25597387.

5: Califf RM. LCZ696: too good to be true? Eur Heart J. 2015 Feb 14;36(7):410-2. doi: 10.1093/eurheartj/ehu501. Epub 2014 Dec 29. PubMed PMID: 25549727.

6: Athyros VG, Katsiki N, Karagiannis A. Editorial: (New drug (LCZ696) for the treatment of heart failure with reduced ejection fraction after 10 years. Can one study change the guidelines?). Curr Vasc Pharmacol. 2014;12(6):867-9. PubMed PMID: 25516014.

7: McMurray J, Packer M, Desai A, Gong J, Greenlaw N, Lefkowitz M, Rizkala A, Shi V, Rouleau J, Solomon S, Swedberg K, Zile MR, Andersen K, Arango JL, Arnold M, Bĕlohlávek J, Böhm M, Boytsov S, Burgess L, Cabrera W, Chen CH, Erglis A, Fu M, Gomez E, Gonzalez A, Hagege AA, Katova T, Kiatchoosakun S, Kim KS, Bayram E, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires F, Refsgaard J, Senni M, Sibulo AS Jr, Silva-Cardoso J, Squire I, Starling RC, Vinereanu D, Teerlink JR, Wong R; on behalf of the PARADIGM-HF Committees and Investigators. A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure. Eur Heart J. 2014 Nov 21. pii: ehu455. [Epub ahead of print] PubMed PMID: 25416329; PubMed Central PMCID: PMC4328198.

8: von Lueder TG, Wang BH, Kompa AR, Huang L, Webb R, Jordaan P, Atar D, Krum H. 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. doi: 10.1161/CIRCHEARTFAILURE.114.001785. Epub 2014 Oct 31. PubMed PMID: 25362207.

9: Jhund PS, Claggett BL, Voors AA, Zile MR, Packer M, Pieske BM, Kraigher-Krainer E, Shah AM, Prescott MF, Shi V, Lefkowitz M, McMurray JJ, Solomon SD; PARAMOUNT Investigators. Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696. Circ Heart Fail. 2014 Nov;7(6):953-9. doi: 10.1161/CIRCHEARTFAILURE.114.001427. Epub 2014 Oct 2. PubMed PMID: 25277997.

10: Lim GB. Heart failure: LCZ696--a PARADIGM shift in treatment for heart failure. Nat Rev Cardiol. 2014 Nov;11(11):618. doi: 10.1038/nrcardio.2014.139. Epub 2014 Sep 16. PubMed PMID: 25223453.

11: Jhund PS, Claggett B, Packer M, Zile MR, Voors AA, Pieske B, Lefkowitz M, Shi V, Bransford T, McMurray JJ, Solomon SD. Independence of the blood pressure lowering effect and efficacy of the angiotensin receptor neprilysin inhibitor, LCZ696, in patients with heart failure with preserved ejection fraction: an analysis of the PARAMOUNT trial. Eur J Heart Fail. 2014 Jun;16(6):671-7. doi: 10.1002/ejhf.76. Epub 2014 Apr 1. PubMed PMID: 24692284.

12: Kario K, Sun N, Chiang FT, Supasyndh O, Baek SH, Inubushi-Molessa A, Zhang Y, Gotou H, Lefkowitz M, Zhang J. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study. Hypertension. 2014 Apr;63(4):698-705. doi: 10.1161/HYPERTENSIONAHA.113.02002. Epub 2014 Jan 20. PubMed PMID: 24446062.

13: Voors AA, Dorhout B, van der Meer P. The potential role of valsartan + AHU377 ( LCZ696 ) in the treatment of heart failure. Expert Opin Investig Drugs. 2013 Aug;22(8):1041-7. doi: 10.1517/13543784.2013.797963. Epub 2013 May 10. Review. PubMed PMID: 23663006.

14: Mearns BM. Phase II PARAMOUNT trial of LCZ696. Nat Rev Cardiol. 2012 Nov;9(11):612. doi: 10.1038/nrcardio.2012.134. Epub 2012 Sep 11. PubMed PMID: 22965107.

15: Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, Shi V, Bransford T, Takeuchi M, Gong J, Lefkowitz M, Packer M, McMurray JJ; Prospective comparison of ARNI with ARB on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) Investigators. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012 Oct 20;380(9851):1387-95. doi: 10.1016/S0140-6736(12)61227-6. Epub 2012 Aug 26. PubMed PMID: 22932717.

16: Lucchese B. Hypertension: LCZ696, a novel dual inhibitor of neprilysin and the angiotensin II receptor, shows promise in phase II trial. Nat Rev Nephrol. 2010 Jul;6(7):383. doi: 10.1038/nrneph.2010.72. PubMed PMID: 20597156.

17: Ruilope LM, Dukat A, Böhm M, Lacourcière Y, Gong J, Lefkowitz MP. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet. 2010 Apr 10;375(9722):1255-66. doi: 10.1016/S0140-6736(09)61966-8. Epub 2010 Mar 16. PubMed PMID: 20236700.

18: Waeber B, Feihl F. Blood-pressure reduction with LCZ696. Lancet. 2010 Apr 10;375(9722):1228-9. doi: 10.1016/S0140-6736(10)60363-7. Epub 2010 Mar 16. PubMed PMID: 20236699.

19: Gu J, Noe A, Chandra P, Al-Fayoumi S, Ligueros-Saylan M, Sarangapani R, Maahs S, Ksander G, Rigel DF, Jeng AY, Lin TH, Zheng W, Dole WP. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010 Apr;50(4):401-14. doi: 10.1177/0091270009343932. Epub 2009 Nov 23. PubMed PMID: 19934029.