Sacubitril hemicalcium salt 是一种有效的NEP抑制剂，IC50=5 nM。它是研究心力衰竭药物 LCZ696 的组分之一。

AHU-377 hemicalcium salt is a potent NEP inhibitor with an IC50 of 5 nM. AHU-377 is a component of the heart failure medicine LCZ696. AHU377 is a prodrug of LBQ657, which is an inhibitor of the zinc metallopeptidase neprilysin. Neprilysin degrades a variety of vasoactive peptides such as atrial and brain natriuretic peptide, bradykinin, adrenomedullin, and endothelin-1. Inhibition of neprilysin leads to an increased level of these peptides and, thus, antihypertensive effects. Formulations containing AHU377 in combination with the angiotensin II receptor antagonist valsartan are used to treat hypertension and heart failure.

AHU377 is converted by enzymatic cleavage of the ethyl ester into the active neprilysin inhibiting metabolite LBQ657. The inactive NEPi precursor, AHU377, does not inhibit collagen accumulation in fibroblasts nor cardiac myocyte hypertrophy. In cardiac fibroblasts, the active NEPi LBQ657 had no discernible effects. In contrast, LBQ657 modestly inhibits cardiac myocyte hypertrophy.

In humans, AHU377 (tmax 0.5-1.1 h) are absorbed quickly. AHU377 is converted rapidly into LBQ657 with its tmax being reached in 1.9-3.5 h. Mean t1/2 values for the biologically active LBQ657 is 9.9-11.1 h.In vehicle-treated dogs, ANF increases urinary sodium excretion from 17.3±3.6 to 199.5±18.4 pequivkglmin. This effect is potentiated significantly in animals which receive AHU377.

1369773-39-6

C48H56CaN2O10

861.058

AHU-377 (hemicalcium salt);AHU377 calcium salt;LCZ696中间体

DMSO:54 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years