| 产品描述： | Sacubitril (AHU-377) is a potent and orally active NEP (neprilysin) inhibitor with an IC50 of 5 nM. Sacubitril is a component of the heart failure medicine LCZ696. Sacubitril can be used for the research of heart failure, hypertension and COVID-19 |
| 靶点： |
IC50: 5 nM (NEP) |
| 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 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 |
| 参考文献： |
1. Ksander GM, et al. Dicarboxylic acid dipeptide neutral endopeptidase inhibitors. J Med Chem. 1995 May 12;38(10):1689-700. 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. 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. 4. Hegde, L.G., et al. Comparative efficacy of AHU-377, a potent neprilysin inhibitor, in two rat models of volume-dependent hypertension. BMC Pharmacol 11, P33 (2011). |
| 溶解性： |
Soluble in DMSO、H2O |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.43 ml |
12.151 ml |
24.302 ml |
| 5 mM |
0.486 ml |
2.43 ml |
4.86 ml |
| 10 mM |
0.243 ml |
1.215 ml |
2.43 ml |
| 50 mM |
0.049 ml |
0.243 ml |
0.486 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京