Sacubitril

Sacubitril is a neprilysin inhibitor used in combination with valsartan for the treatment of heart failure. As a prodrug, Sacubitril is activated to LBQ657 by de‑ethylation via esterases, and the active metabolite inhibits neprilysin, the enzyme responsible for the degradation of natriuretic peptides. Sacubitril is supplied as a solid with a purity of ≥98% (HPLC). The biphenyl framework and the chiral center of Sacubitril are critical for its potent neprilysin inhibitory activity. Sacubitril is also available as a reference standard for analytical method development, method validation, quality control applications, and ANDA filings.

 

  Product Parameters

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Parameter	Specification
Product Name	Sacubitril
CAS Number	149709-62-6
Molecular Formula	C₂₄H₂₉NO₅
Molecular Weight	411.49 g/mol
Physical Form	Solid
Appearance	White to offwhite powder
Boiling Point	656.9±55.0℃
Density	1.151±0.06 g/cm3
Storage Condition	Store at –20°C

 

Pharmacological Action

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AHU377 and the angiotensin II AT1 receptor antagonist valsartan are combined in a 1:1 molar ratio to form LCZ696, a dual inhibitor of angiotensin II (AT2) receptors and neprilysin receptors. Its antihypertensive efficacy surpasses that of standard antihypertensive drugs, making it a novel therapeutic agent for heart failure. AHU377 is a prodrug that can be converted into its active form, LBQ657 ethyl ester. Current Phase III clinical trials have demonstrated superior efficacy and safety profiles compared to the benchmark drug enalapril. In clinical trials, this combination therapy was administered to patients with mild to moderate hypertension in a double-blind Phase II study, comprising doses ranging from 100 to 400 mg of the combination drug, 80 to 320 mg of valsartan, 200 mg of a neprilysin inhibitor, or a placebo. The combined regimen exhibited more pronounced efficacy than valsartan alone, with excellent tolerability and no reports of angioedema. LCZ696 has demonstrated sustained therapeutic benefits from early treatment stages.

(1) The risk of death from cardiovascular diseases was reduced by 20% (p=0.00004).

(2) The hospitalization rate for heart failure decreased by 21% (p=0.00004).

(3) The all-cause mortality risk was reduced by 16% (p=0.0005).

(4) Overall, when comprehensively evaluating the primary endpoint of cardiovascular death or hospitalization for heart failure, there was a 20% reduction in risk (p=0.0000002).

 

Market A nalysis

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In the field of drug development, most successful Phase II drug candidates invariably attract a wave of competing projects. LCZ696's exceptional performance has stunned the industry, and it is predicted that no drug in the cardiovascular field will be able to rival it in the coming years. Some analysts estimate its peak sales could reach $8 billion, while Deutsche Bank analysts predict $6 billion based on its superior efficacy in reducing key cardiovascular risks. Although figures vary slightly, there is no doubt that LCZ696 will become a blockbuster drug that will usher cardiovascular therapy into a new era.

 

Bioactivity

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Sacubitril (AHU-377) is an effective NEP inhibitor with an IC50 value of 5 nM. It serves as a component of the heart failure drug LCZ696.

 

Contact Us

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Need a trusted supplier of Sacubitril for your heart failure drug manufacturing or analytical development program? Cosperpharm is ready to support your project. Contact our team today for pricing, documentation, or technical support — we are committed to delivering excellence in pharmaceutical intermediates and reference standards.