AHU-377

• CAT Number: I001848
• CAS Number: 149709-62-6
• Molecular Formula: C₂₄H₂₉NO₅
• Molecular Weight: 411.49
• Purity: ≥95%
• Synonyms: Sacubitril sodium; AHU377; AHU 377; AHU-377; LCZ696.
• Target: Neprilysin
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 5.0 nM
• InChI: InChI=1S/C24H29NO5/c1-3-30-24(29)17(2)15-21(25-22(26)13-14-23(27)28)16-18-9-11-20(12-10-18)19-7-5-4-6-8-19/h4-12,17,21H,3,13-16H2,1-2H3,(H,25,26)(H,27,28)/t17-,21+/m1/s1
• InChIKey: PYNXFZCZUAOOQC-UTKZUKDTSA-N
• SMILES: CCOC(=O)C(C)CC(CC1=CC=C(C=C1)C2=CC=CC=C2)NC(=O)CCC(=O)O

AHU-377(CAT: I001848), also known as sacubitril, is a drug used in the treatment of heart failure. It is a prodrug that is rapidly converted to its active metabolite, LBQ657, by esterases in the body. LBQ657 is an inhibitor of neprilysin, an enzyme that breaks down various vasoactive peptides, including natriuretic peptides, bradykinin, and adrenomedullin. By inhibiting neprilysin, AHU-377 increases the levels of these peptides, which can result in vasodilation, natriuresis, and diuresis, ultimately improving cardiac function in heart failure patients. AHU-377 is often used in combination with the angiotensin II receptor blocker valsartan (known as sacubitril/valsartan or Entresto) for the treatment of heart failure with reduced ejection fraction.

Reference

1. Expert Opin Investig Drugs. 2013 Aug;22(8):1041-7. doi:
10.1517/13543784.2013.797963. Epub 2013 May 10.

The potential role of valsartan + AHU377 ( LCZ696 ) in the treatment of heart
failure.

Voors AA(1), Dorhout B, van der Meer P.

Author information:
(1)Professor of Cardiology, University of Groningen, University Medical Center
Groningen, Department of Cardiology, Groningen, The Netherlands.

INTRODUCTION: Heart failure remains a syndrome with a very high mortality rate
and a poor quality of life. For patients with heart failure and a preserved
ejection fraction (HFpEF), no drugs have shown to improve mortality and
morbidity, and therefore novel drugs are highly needed. LCZ696 , a first in class
angiotensin receptor neprilysin inhibitor (ARNi), might be an interesting novel
drug for the treatment of heart failure.
AREAS COVERED: Previous studies have shown promising effects of a combination
drug with a neutral endopeptidase and an angiotensin-converting enzyme inhibitor
(omapatrilat) for the treatment of patients with heart failure. However, the
occurrence of angioedema prevented the drug from further development. The
majority of this paper will discuss the metabolism, pharmacokinetics,
pharmacodynamics, clinical effects, and safety of LCZ696, with a particular focus
on heart failure.
EXPERT OPINION: LCZ696 is superior to valsartan alone in reducing blood pressure.
Preliminary results from a Phase II trial showed that LCZ696 reduced NT-proBNP to
a greater extent than valsartan alone, and in addition LCZ696 had beneficial
effects on symptoms. With these promising first results, the results of ongoing
further studies in heart failure are eagerly awaited.