LCZ696

한글명:LCZ696

카스 번호936623-90-4

상품명:LCZ696

CBNumberCB72715242

분자식C48H58N6O8

포뮬러 무게847.03

MOL 파일936623-90-4.mol

화학적 성질

저장 조건	Store at -20°C
용해도	≥45.05 mg/mL in DMSO; ≥11.28 mg/mL in H2O; ≥28.5 mg/mL in EtOH
물리적 상태	고체
물리적 상태	단단한 모양
색상	White to light yellow
InChIKey	XTKIDERFOUYBDE-NOFROVMTNA-N
SMILES	C(C1C=CC(C2C=CC=CC=2C2=NN=NN2)=CC=1)N(C(=O)CCCC)[C@H](C(=O)O)C(C)C.C(C1C=CC(C2C=CC=CC=2)=CC=1)[C@@H](NC(=O)CCC(=O)O)C[C@@H](C)C(=O)OCC \|&1:25,45,55,r\|

그림문자(GHS)

LCZ696 화학적 특성, 용도, 생산

개요
LCZ696 is a dual angiotensin II receptor antagonist and neprilysin inhibitor that is a combination of the nonpeptide angiotensin II receptor antagonist valsartan and AHU377 , a prodrug of LBQ657 , which is an inhibitor of the zinc metallopeptidase neprilysin., LCZ696 (2-60 mg/kg) induces a dose-dependent decrease in mean arterial pressure in rats expressing human renin and angiotensinogen, a double-transgenic model for angiotensin II-dependent hypertension. Formulations containing LCZ696 are under clinical investigation for the treatment of mild to moderate hypertension and chronic heart failure.
Mechanism of action
LCZ696 is a molecule that combines the moieties of valsartan and sacubitril (the neprilysin inhibitor) in a single substance. By inhibiting neprilysin, the degradation of natriuretic peptides, bradykinin, and other peptides is slowed. Hence, high circulating levels of natriuretic peptides enhance diuresis , natriuresis, myocardial relaxation, and anti-remodelling, on top of the ARB effects of valsartan.
Clinical Use
LCZ696 (Novartis Pharmaceuticals), a first-in-class inhibitor of dualacting angiotensin-2 type-I receptor and neprilysin inhibitors, was developed as a molecule composed of molecular moieties of valsartan and neprilysin inhibitor prodrug AHU377 in a 1:1 ratio. Several phase 2 randomised clinical trials have been done or are underway in patients with hypertension. In a proof-of-concept randomised trial, LCZ696 was compared with valsartan in 1328 patients with mild-to-moderate hypertension, and provided fully additive reduction of blood pressure. No cases of angio-oedema were reported in the 8 week treatment period. This tolerance should be confirmed, particularly in black patients, for whom omapatrilat resulted in a higher occurrence of angio-oedema than in white patients. Indeed, in the proof-of-concept trial only about 8% of patients were black.
참고 문헌
1. McMurray, John J. V. et al. “Angiotensin-neprilysin inhibition versus enalapril in heart failure.” The New England journal of medicine 371 11 (2014): 993-1004. DOI: 10.1056/NEJMoa1409077
2. Gu, Jessie et al. “Pharmacokinetics and Pharmacodynamics of LCZ696, a Novel Dual‐Acting Angiotensin Receptor—Neprilysin Inhibitor (ARNi).” The Journal of Clinical Pharmacology 50 (2010): n. pag. DOI: 10.1177/0091270009343932
3. Langenickel, T.H., & Dole, W.P. (2012). Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discovery Today: Therapeutic Strategies, 9. DOI: 10.1016/J.DDSTR.2013.11.002
4. Suematsu, Yasunori et al. “LCZ696, an angiotensin receptor–neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin‐induced diabetic mice.” European Journal of Heart Failure 18 (2016): n. pag. DOI: 10.1002/ejhf.474

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