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936623-90-4

936623-90-4 Structure

936623-90-4 Structure
IdentificationBack Directory
[Name]

LCZ696
[CAS]

936623-90-4
[Synonyms]

LZC696
Entresto
LCZ696 Entresto
LCZ696 interMediate
Valsartan/sacubitril
Valsartan-sacubitril(LCZ696)
Sacubitril mixture with Valsartan
Cocrystal of Sacubitril and Valsartan
[(C24H29N5O3).(C24H29NO5).2.5(H2O).3Na]
4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoate
(S)-2-(N-((2'-(1H-Tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)hexanamido)-3-methylbutanoic acid
3-(1-Biphenyl-4-ylMethyl-3-ethoxycarbonyl-1-butylcarbaMoyl)propionate-3'-Methyl-2'-(pentanoyl(2'-(tetrazol-5-ylate)biphenyl-4'-ylMethyl)aMino)butyrate
N-(1-oxopentyl)-N-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine, compd. with α-ethyl (αR,γS)-γ-[(3-carboxy-1-oxopropyl)amino]-α-methyl[1,1'-biphenyl]-4-pentanoate, sodium salt, hydrate (2)
[EINECS(EC#)]

-0
[Molecular Formula]

2(C24H29N5O3).2(C24H29NO5).5(H2O).6Na
Questions And AnswerBack Directory
[Drugs for heart failure]

LCZ696 a drug developed by Novartis Pharmaceutical of the United States for the treatment of heart failure. Heart failure is a life-threatening disease. The patient's heart cannot pump enough blood to supply the body, and appear the symptoms of dyspnea, fatigue and fluid retention slowly, then gradually increased, significantly affect the quality of life.
LCZ696 is a dual-acting angiotensin-receptor enkephalinase inhibitor that has a unique mechanism that is thought to reduce the strain of failing hearts. LCZ696 can enhance the body's natural defense against heart failure, as well as increase the level of natriuretic peptides and other endogenous vasoactive peptides, and inhibit the renin-angiotensin-aldosterone system (RAAS). LCZ696 has combined with Novartis's Hypertension Medication (Diovan, generic name: valsartan) and the experimental drug AHU-377. AHU377 blocks the mechanism of the two peptides responsible for lowering blood pressure. Diovan improves vasodilatation and stimulates the body to excrete sodium and water.
The safety threshold of cardiovascular drugs is extremely high, and LCZ696 even shows a higher safety than conventional drugs. Previously, Novartis vigorously develop the cardiovascular drug— serelaxi, while because of security issues, both the FDA and the European Union did not grant this drug. This is undoubtedly a heavy blow to Novartis. However, the success of LCZ696 will pay back Novartis a big era in the cardiovascular field.。
In August 2014, Novartis announced significant results as a landmark of PARADIGM-HF trial. LCZ696 was significantly superior to the ACE inhibitor Enalapril at several key end points, including a significant reduction in cardiovascular death risk or heart failure hospitalization rate. These latest analyzes were first disclosed at the American Heart Association Scientific Conference in 2014 and published in Circulation at the same time.
On November 30, 2014, the European Medicines Agency (EMP) Committee for Medicinal Products for Human Use (CHMP) has granted LCZ696 an accelerated eligibility, so it became the first cardiovascular drug to qualify for accelerated evaluation in the history of EU drug regulation. Prior to this, the EU's Accelerated Assessment of Qualifications was never granted to the cardiovascular field.
LCZ696 is an experimental drug developed for the treatment of patients with Heart Failure with reduced Ejection Fraction (HFrEF). Accreditation of Accelerated Evaluation by CHMP means that the review time of LCZ696 will be shortened by 60 days in official EU. Novartis is expected to submit LCZ696 application approval (MAA) in the European Union at the beginning of 2015. The MAA submission will be based on data from the landmark Phase III PARADIGM-HF study, which is the largest study of heart failure patients conducted in the history. The data show that the efficacy and safety of LCZ696 is beyond the clinical standard drug enalapril (enalapril), including significantly reduced cardiovascular death or heart failure hospitalization risk
The industry believes that LCZ696's outstanding performance, make it became one of the most important progress over the past 10 years in the field of cardiology. At the same time, in the next few years, there will be no drug to compete with the LCZ696 in the cardiovascular field. Some analysts predict that the LCZ696 sales peaked at $ 8 billion; while Deutsche Bank analysts expect the drug to peak at $ 6 billion, given LCZ696's superior performance in reducing cardiovascular risk. Although the data are slightly different, but there is no doubt that, LCZ696 will become a super star for Novartis. In addition to bring rolling financial resources, it will lead the cardiovascular treatment step into a new era.
In February 2015, Novartis Pharma Test Drug LCZ696 was given priority review by the US Food and Drug Administration (FDA) for the treatment of Heart Failure with reduced Ejection Fraction (HFrEF). Novartis added that the drug's overall review time will be reduced by 8 months, the FDA may make its approval decision in August.
Novartis said its listing application in US was based on a 3-phase PARADIGM-HF study, which showed a significant reduction in cardiovascular mortality and heart failure hospitalization compared with the ACE inhibitor Enalapril.
This information is compiled and edited by Nan, Xiao Nan from ChemicalBook.
[bioactivity]

LCZ696, composed of valsartan and sacubitril in a 1: 1 molar ratio, is an orally bioavailable, dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) for the treatment of hypertension and heart failure.
[In vivo studies]

In a double transgenic, overexpressed human renin, angiotensinogen and plasma atrial natriuretic peptide immunoreactivity rat, LCZ696 (60 mg/kg p.o.) induced a persistent decrease and dose-dependence in mean arterial pressure (MAP) and , and stimulated dose-dependent rapid increase of ANP immunoreactivity in plasma. LCZ696 (68 mg/kg p.o.) attenuates cardiac remodeling and dysfunction by reducing myocardial fibrosis and cardiac hypertrophy in a rat myocardial infarction (MI) model.
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