AHU-377 (heMicalciuM salt)

China [CN]

Core Pharmacology and Applications

Mechanism of Action: It is a prodrug with no significant activity on its own. After entering the body, it is hydrolyzed by esterases into the active metabolite LBQ657. LBQ657 potently inhibits neprilysin (IC₅₀ value of 5 nm), preventing the degradation of natriuretic peptides such as atrial natriuretic peptide and brain natriuretic peptide, which have antihypertensive effects. This ultimately leads to vasodilation, reduced blood pressure, and decreased cardiac load.

Clinical Applications: It is combined with the angiotensin II AT1 receptor antagonist valsartan in a 1:1 molar ratio to form the combination drug sacubitril/valsartan (brand name Entresto). This combination drug, as an angiotensin receptor-neprilysin inhibitor, is an important medication for the treatment of heart failure. Compared to traditional drugs, it significantly reduces the risk of cardiovascular death and hospitalization due to heart failure in patients.