Sacubitril/valsartan (LCZ696)

Catalog No.S7678 Synonyms: Sacubitril, Valsartan

Sacubitril/valsartan (LCZ696) Chemical Structure

Molecular Weight(MW): 915.98

Sacubitril/valsartan (LCZ696), consisting of valsartan and sacubitril in 1:1 molar ratio, is an orally bioavailable, dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) for hypertension and heart failure. Phase 3.

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Cited by 2 Publications

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  • Histological analysis staining of three groups. (a) Representative H&E-staining micrographs displaying transverse myocardial section (original magnification ×200). (b) Masson staining of three groups (original magnification ×200). Collagen content (%) of heart tissues were presented as fibrosis (***P < 0.001, n = 7 per group). (c) Cardiac section of three group mice hearts stained with WGA (original magnification ×400) (*P < 0.05, n = 7 per group). (d) The expression of Drp1 significantly increased in DOX group (***P < 0.001, n = 7 per group) and it decreased in DOX + LCZ696 group (**P < 0.01, n = 7 per group).

    J Mol Cell Cardiol, 2017, 108:138-148. Sacubitril/valsartan (LCZ696) purchased from Selleck.

    Representative H&E stain of heart sections from (A) sham-operated group, (B) model group, (C) LCZ696-treated group. Representative H&E-staining micrographs displaying transverse myocardial section (original magnification ×100).

    RSC Adv, 2017, doi:10.1039/C7RA01404J. Sacubitril/valsartan (LCZ696) purchased from Selleck.

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Biological Activity

Description Sacubitril/valsartan (LCZ696), consisting of valsartan and sacubitril in 1:1 molar ratio, is an orally bioavailable, dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) for hypertension and heart failure. Phase 3.
Targets
RAAS [1]
Assay
Methods Test Index PMID
Western blot
p-AMPKα / AMPKα / p-AKT / AKT / p-eNOS / eNOS ; 

PubMed: 28178430     


Effects of valsartan (10 µmol/L) on Akt, adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) phosphorylation and expression in human umbilical vein endothelial cells. Ctrl: control; Antibodies: p-AMPKα (Thr172) - phospho-AMPKα (Thr172), AMPKα, p-Akt (Ser473) - phospho-Akt (Ser473), Akt, p-eNOS (Ser1177) - phospho-eNOS (Ser1177), eNOS, and beta-actin.

p-LKB1 / t-LKB1 / p-AMPK / t-AMPK / p-ACC / t-ACC ; 

PubMed: 25109475     


To confirm that valsartan activates AMPK through LKB1, THP-1 cells were transfected with LKB1 siRNA or scrambled siRNA and incubated with valsartan for 24 hrs. The proteins were quantified and Western blot analysis was performed with corresponding antibodies (P-AMPK, AMPK, p-LKB1, LKB1, p-ACC and ACC). The relative intensity of each protein is depicted as bar graphs on the right side

28178430 25109475
In vivo In double-transgenic rats overexpressing human renin and angiotensinogen and plasma atrial natriuretic peptide immunoreactivity, LCZ696 (60 mg/kg p.o.) induces a dose-dependent and long-lasting reduction in mean arterial pressure (MAP), and stimulates a rapid and dose-dependent augmentation of plasma ANP immunoreactivity. [1] In rat myocardial infarction (MI) model, LCZ696 (68 mg/kg p.o.) attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. [2]

Protocol

Animal Research:

[2]

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  • Animal Models: Double-transgenic rats overexpressing human renin and angiotensinogen and plasma atrial natriuretic peptide immunoreactivity
  • Formulation: --
  • Dosages: ~60 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro Water 100 mg/mL warmed (109.17 mM)
DMSO 30 mg/mL warmed (32.75 mM)
Ethanol 9 mg/mL warmed (9.82 mM)

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 915.98
Formula

C24H29N5O3.C24H29NO5.5/2H2O.3Na

CAS No. 936623-90-4
Storage powder
in solvent
Synonyms Sacubitril, Valsartan

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02690974 Completed Drug: LCZ696 (sacubitril/valsartan) Hearth Failure With Reduced Ejection Fraction (HFrEF) Novartis Pharmaceuticals|Novartis March 8 2016 Phase 4
NCT02661217 Completed Drug: LCZ696 Heart Failure With Reduced Ejection Fraction Novartis Pharmaceuticals|Novartis February 12 2016 Phase 4
NCT02226120 Completed Drug: LCZ696 Chronic Heart Failure With Reduced Ejection Fraction Novartis Pharmaceuticals|Novartis October 16 2014 Phase 3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID