Sacubitril (AHU-377) is a potent NEP inhibitor with an IC50 of 5 nM. Sacubitril (AHU-377) is a component of the heart failure medicine LCZ696.
体外研究
Sacubitril (AHU-377) is a single molecule that is comprised of molecular moieties of valsartan, an ARB, and Sacubitril (AHU-377), 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 (AHU-377), 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.
体内研究
In humans, Sacubitril (AHU-377) (tmax 0.5-1.1 h) are absorbed quickly. Sacubitril (AHU-377) 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 Sacubitril (AHU-377). Urinary volume is also potentiated in animals which receive an iv administration of Sacubitril (AHU-377).
分子式
C24H29NO5
分子量
411.49
CAS号
149709-62-6
中文名称
沙库必曲
运输条件
Room temperature in continental US; may vary elsewhere.