AHU-377

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AHU-377 是一种有效的 NEP 抑制剂，IC50 为 5 nM。 AHU-377 是心力衰竭化合物 LCZ696 的成分。

AHU-377 is a potent NEP inhibitor with an IC50 of 5 nM. AHU-377 is a component of the heart failure medicine LCZ696.(In Vitro):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.(In Vivo):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).In normotensive rats, pretreatment with Sacubitril (3, 10 and 30 mg/kg, PO.) augments ANP-evoked plasma cGMP levels by 2.4, 3.3 and 4.0 fold, respectively (4h AUC compared to vehicle).Sacubitril (30 and 100 mg/kg, PO) produces a dose-dependent antihypertensive effect in Dahl-SS rats.

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.

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).In normotensive rats, pretreatment with Sacubitril (3, 10 and 30 mg/kg, PO.) augments ANP-evoked plasma cGMP levels by 2.4, 3.3 and 4.0 fold, respectively (4h AUC compared to vehicle).Sacubitril (30 and 100 mg/kg, PO) produces a dose-dependent antihypertensive effect in Dahl-SS rats.

AHU-377

Proteasome/Ubiquitin

Serine Protease

Neprilysin

Cardiovascular Disease

——

149709-62-6

411.49

C24H29NO5

>98% (HPLC)

DMSO : ≥ 100 mg/mL 243.02 mM; H2O : < 0.1 mg/mL

CCOC(=O)[C@H](C)C[C@@H](Cc1ccc(cc1)-c1ccccc1)NC(=O)CCC(O)=O

——

(-20℃)

With Ice Pack

≥ 2 years