LCZ696(Sacubitril + Valsartan)
API’s Name：LCZ696(Sacubitril + Valsartan)
CAS No.：936623-90-4
Indication：Heart failure
Innovator：
Specification：In-House
US DMF：√
EU DMF ：
CEP：
Only for R&D purpose
Product Detail
Intermediates
Code | CAS | Specification |
LCZ-4 | 1426129-50-1 | In-House |
LCZ-7 | 1012341-48-8 | In-House |
LCZ-8 | 1012341-50-2 | In-House |
LCZ-9 | 149690-12-0 | In-House |
Description
LCZ696 (Sacubitril/Valsartan), comprised Valsartan (an ARB) and Sacubitril (AHU377) in 1:1 molar ratio, is a first-in-class, orally bioavailable, and dual-acting angiotensin receptor-neprilysin (ARN) inhibitor for hypertension and heart failure[1][2][3]. LCZ696 ameliorates diabetic cardiomyopathy by inhibiting inflammation, oxidative stress and apoptosis.
Background
LCZ696 is a first in class ARNi (angiotensin receptor neprilysin inhibitor) comprising anionic moieties of AR valsartan and the neprilysin inhibitor prodrug AHU377 (1:1 ratio) for heart failure and hypertension.
The angiotensin receptors are G-protein-coupled receptors. They mediate the cardiovascular and other effects of angiotensin II which is a bioactive peptide of the renin–angiotensin system. Neprilysin is a neutral endopeptidase that degrades endogenous vasoactive peptides such as natriuretic peptides. Inhibition of neprilysin increases the natriuretic peptides concentration that contributed to cardiac, vascular and renal protection. [1]
In Sprague-Dawley rats, oral administration of LCZ696 led to a dose-dependent rise in immunoreactivity of atrial natriuretic peptide resulting from neprilysin inhibition. In hypertensive double transgenic rats, LCZ696 caused a dose-dependent and sustained reduction in mean arterial pressure. A healthy participants, a randomized, double-blind, placebo-controlled study confirmed that LCZ696 provided concurrent neprilysin inhibition and AT1 receptor blockade. LCZ696 was safe and well tolerated in human. [2] [3]
References:
McMurray JJ, Packer M, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004.
Gu J, Noe A, Chandra P, Al-Fayoumi S et al. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010 Apr;50(4):401-14.
Langenickel TH, Dole WP. Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure, Drug Discov Today: Ther Strategies (2014),
Storage
| Powder | -20°C | 3 years |
4°C | 2 years | |
| In solvent | -80°C | 6 months |
-20°C | 1 month |
Chemical structure
