A first in class ARNi (angiotensin receptor neprilysin inhibitor)
CAS：936623-90-4
分子式：C48H54N6Na3O8.2.5H2O
分子量：956.99
纯度：98%
存储：Store at -20°C

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]

参考文献:
[1].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.
[2].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.
[3].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),