Sacubitril is a prodrug that is converted to the active form LBQ657. What is the enzymatic target of LBQ657 and what is the pharmacodynamic consequence?

• A Inhibits angiotensin-converting enzyme (ACE), reducing angiotensin II and aldosterone
• B Inhibits neprilysin, preventing degradation of natriuretic peptides (BNP, ANP), bradykinin and angiotensin II ✓
• C Blocks aldosterone receptor, reducing sodium retention in the collecting duct
• D Inhibits angiotensin II receptor type 1 (AT1), reducing vasoconstriction

Explanation

Sacubitril is an ester prodrug hydrolysed to LBQ657, which inhibits neprilysin — a neutral endopeptidase that degrades natriuretic peptides (ANP, BNP), bradykinin, angiotensin II, and substance P. Neprilysin inhibition raises natriuretic peptide levels, promoting natriuresis, vasodilation, and anti-fibrotic effects; however, it also raises angiotensin II, which is why sacubitril is combined with valsartan (ARB) as sacubitril/valsartan (LCZ696) for heart failure with reduced ejection fraction.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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