GLPBio

LCZ696

Catalog No.: GC11784Purity:>99.50%
LCZ696, a combination of prodrug sacubitril and valsartan at equal molar ratios, is an oral active angiotensin II receptor-neprilysin inhibitor.

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LCZ696
Cas No.: 936623-90-4
10mM (in 1mL DMSO)In Stock
$114.00
1
1mgIn Stock
$31.00
1
5mgIn Stock
$77.00
1
10mgIn Stock
$109.00
1
25mgIn Stock
$192.00
1
50mgIn Stock
$279.00
1
100mgIn Stock
$414.00
1

Citations

1 publicationsPublications from researchers using this product

Description

LCZ696, a combination of prodrug sacubitril and valsartan at equal molar ratios, is an oral active angiotensin II receptor-neprilysin inhibitor [1]. After ingestion, LCZ696 undergoes rapid dissociation into valsartan and sacubitril, which cause neprilysin inhibition and AT1 receptor blockade, resulting increases in ANP, plasma and urinary cGMP, renin concentration and activity [2]. LCZ696 has been widely used to improve heart and kidney functions and to induce memory and cognitive dysfunction in animals [3].

In vitro, LCZ696 treatment (20µM) for 24 hours significantly reduced the production of reactive oxygen species (ROS) and the level of malondialdehyde (MDA) in human umbilical vein endothelial cells (HUVECs), thereby alleviating the oxidative stress induced by Lipopolysaccharide (LPS) [4]. Treatment with 10µM LCZ696 for 24 hours reduced apoptosis-related events and increased the survival rate of podocytes cultured in high glucose conditions[5]. Treatment with 1µM LCZ696 for 3 hours significantly reduced the expression of ANP, βMHC, and TIMP2 in cardiomyocytes, inhibited the increase in cardiomyocyte size caused by angiotensin II, and promoted the protein expression of ACE2[6].

In vivo, LCZ696 treatment via oral administration at a dose of 68mg/kg/day for 4 weeks significantly reduced cardiac remodeling and dysfunction in rats after myocardial infarction[7]. For 8 consecutive weeks, an oral dose of 60mg/kg of LCZ696 was administered daily, significantly improving the biochemical, morphological, and molecular biological indicators of renal injury in mice with cardiorenal syndrome[8].

References:
[1] Minguet J, Sutton G, Ferrero C, et al. LCZ696: a new paradigm for the treatment of heart failure?[J]. Expert Opinion on Pharmacotherapy, 2015, 16(3): 435-446.
[2] Menendez J T. The mechanism of action of LCZ696[J]. Cardiac failure review, 2016, 2(1): 40.
[3] Poorgolizadeh E, Moghadam F H, Dormiani K, et al. Do neprilysin inhibitors walk the line? Heart ameliorative but brain threatening![J]. European journal of pharmacology, 2021, 894: 173851.
[4] Gao A, Wang Y, Gao X, et al. LCZ696 ameliorates lipopolysaccharide-induced endothelial injury[J]. Aging (Albany NY), 2021, 13(7): 9582.
[5] Zhang H, Yu M, Zhang Y, et al. LCZ696 improves oxidative stress injury in human podocytes induced by increased glucose levels via Nrf2/HO-1 signaling pathway[J]. European Journal of Medical Research, 2025, 30(1): 598.
[6] Wang Y, Guo Z, Gao Y, et al. Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy[J]. Cell & Bioscience, 2019, 9(1): 86.
[7] von Lueder T G, Wang B H, Kompa A R, et al. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy[J]. Circulation: Heart Failure, 2015, 8(1): 71-78.
[8] Li Y, Kang L, Rong K, et al. Renal protective effects and mechanisms of the angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome[J]. Life Sciences, 2021, 280: 119692.

Protocol

Cell experiment [1]:

Cell lines

Human umbilical vascular endothelial cells (HUVECs)

Preparation Method

HUVECs were grown in 2% serum endothelial growth media (EGM2) supplied with essential growth factors, 100U/ml penicillin, and 100μg/ml streptomycin at 37°C in 5% CO2/atmosphere. Cells (5×103 cells/ml) were seeded in 96-well plates and allowed to adhere in a 5% CO2 incubator at 37°C overnight. 1μg/ml LPS-containing growth media was added to the confluent HUVECs’ media for 24 hours. Different concentrations of LCZ696 (0, 5, 10, and 20μM) and 1μg/mL LPS were then added to the confluent HUVECs media at the same time for 24 hours. The levels of ROS and MDA were analyzed.

Reaction Conditions

0, 5, 10, and 20μM; 24h

Applications

LCZ696 treatment significantly reduced levels of ROS and MDA induced by LPS within HUVECs in a dose-dependent manner.
Animal experiment [2]:

Animal models

Male C57BL/6 mice

Preparation Method

Eight-week-old male C57BL/6 mice were routinely maintained in a standard environment with food and water ad libitum. The mice were randomly assigned and underwent abdominal aorta ligation or sham surgery. For ligation, using a 27G needle (0.4mm outside diameter), the abdominal aorta was ligated tightly with a 5-0 surgical suture above the renal artery, leading to a 60% reduction in the diameter. For the sham operations, the abdominal aorta was not ligated. The mice with abdominal aortic ligation were randomized into three groups: no treatment (n=8), LCZ696 treatment (n=8), and valsartan treatment (n=8). The mice with sham surgery were the control group (CTL, n=8). The mice in the LCZ696 group were administered 60mg/kg/day LCZ696 dissolved in corn oil by oral gavage for 8 weeks. Both kidneys were removed for analysis.

Dosage form

60mg/kg/day for 8 weeks; p.o.

Applications

LCZ636 treatment significantly attenuated renal injury and mitigated renal fibrosis in mice with abdominal aortic ligation.

References:
[1] Gao A, Wang Y, Gao X, et al. LCZ696 ameliorates lipopolysaccharide-induced endothelial injury[J]. Aging (Albany NY), 2021, 13(7): 9582.
[2] Li Y, Kang L, Rong K, et al. Renal protective effects and mechanisms of the angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome[J]. Life Sciences, 2021, 280: 119692.

Product Documents

Purity:>99.50%Appearance:A solid

Chemical Properties

CAS No.
936623-90-4
SMILES
CCCCC(N([C@@](C([O-])=O)([H])C(C)C)CC1=CC=C(C2=CC=CC=C2C3=N[N-]N=N3)C=C1)=O.CCOC([C@](C[C@@](/N=C([O-])/CCC([O-])=O)([H])CC4=CC=C(C5=CC=CC=C5)C=C4)([H])C)=O.[3Na+].[2.5H2O]
Molecular Formula
C48H54N6Na3O8.2.5H2O
Molecular Weight
956.99
Solubility
≥ 45.05mg/mL in DMSO
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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