Sacubitril is combined with valsartan in heart failure with reduced ejection fraction. The target enzyme inhibited by sacubitril's active metabolite (LBQ657) is:

• A Angiotensin-converting enzyme (ACE)
• B Aldosterone synthase (CYP11B2)
• C Angiotensin II type-1 receptor (AT1R)
• D Neprilysin (neutral endopeptidase, NEP) ✓

Explanation

Sacubitril is a prodrug converted to LBQ657, which inhibits neprilysin. Neprilysin degrades natriuretic peptides (BNP, ANP), bradykinin, and adrenomedullin; its inhibition raises these vasoactive peptides, promoting natriuresis, vasodilation, and anti-fibrotic effects. Valsartan blocks AT1R. Valsartan is combined because neprilysin inhibition alone would excessively raise angiotensin II.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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