Sacubitril hemicalcium salt  (Synonyms: AHU-377 hemicalcium salt)

Sacubitril hemicalcium salt (AHU-377 hemicalcium salt) is a potent NEP inhibitor with an IC₅₀ of 5 nM. Sacubitril hemicalcium salt is a component of the heart failure medicine LCZ696.

IC50: 5 nM (NEP)^[1]

Sacubitril (AHU-377) is a single molecule that is comprised of molecular moieties of valsartan, an ARB, and Sacubitril hemicalcium salt, a neprilysin inhibitor (1:1 ratio). Sacubitril (AHU-377) is converted by enzymatic cleavage of the ethyl ester into the active neprilysin inhibiting metabolite LBQ657^[2]. The inactive NEPi precursor, Sacubitril hemicalcium salt, 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^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In humans, Sacubitril (AHU-377)(t_max 0.5-1.1 h) are absorbed quickly. Sacubitril hemicalcium salt is converted rapidly into LBQ657 with its t_max being reached in 1.9-3.5 h. Mean t_1/2 values for the biologically active LBQ657 is 9.9-11.1 h^[2].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 Sacubitril (AHU-377). Urinary volume is also potentiated in animals which receive an iv administration of Sacubitril (AHU-377)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

430.52

Solid

C₂₄H₂₈Ca_0.5NO₅

1369773-39-6

O=C(CCC([O-])=O)N[[email protected]](CC1=CC=C(C2=CC=CC=C2)C=C1)C[[email protected]@H](C)C(OCC)=O.[0.5Ca2+]

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Ksander GM, et al. Dicarboxylic acid dipeptide neutral endopeptidase inhibitors. J Med Chem. 1995 May 12;38(10):1689-700.  [Content Brief]

  [2]. Voors AA, et al. The potential role of valsartan + AHU377 ( LCZ696 ) in the treatment of heart failure. Expert Opin Investig Drugs. 2013 Aug;22(8):1041-7.  [Content Brief]

  [3]. von Lueder TG, et al. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circ Heart Fail. 2015 Jan;8(1):71-8.  [Content Brief]