1369773-39-6

Name	AHU-377 hemicalcium salt
Synonyms	(alphar AHU-377 hemicalcium salt AHU-377 (heMicalciuM salt) LCZ696(valsartan + sacubitril) impurity 1 Ethyl (αR,γS)-γ-[(3-carboxy-1-oxopropyl)amino]-α-methyl-[1,1'-biphenyl]-4-pentanoate hemicalcium salt Calciumbis(4-{[(1S,3R)-1-([1,1'-biphenyl]-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl] amino} -4-oxobutanoate)
CAS	1369773-39-6

Molecular Formula	C48H56CaN2O10
Molar Mass	861.04364
Melting Point	>140°C (dec.)
Solubility	DMSO (Slightly, Heated), Methanol (Slightly)
Appearance	powder
Color	white to beige
Storage Condition	-20°C
In vitro study	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. 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.
In vivo study	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.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).

UN IDs

UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI: all

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