| 中文名称 | 沙库巴曲 |
| 英文名称 | AHU-377 |
| CAS号 | 149709-62-6 |
| 分子式 | C24H29NO5 |
| 分子量 | 411.49 |
| EINECS号 | 1592732-453-0 |
| 沸点 | 656.9±55.0 °C(Predicted) |
| 密度 | 1.151±0.06 g/cm3(Predicted) |
| 溶解度 | DMSO 中≥41.1 mg/mL;超声检测水中≥21.45 mg/mL; ≥26.85 mg/mL,乙醇溶液,超声波 |
| 形态 | 油状 |
| 酸度系数(pKa) | 4.72±0.10(Predicted) |
| 颜色 | 无色 |
IC50: 5 nM (NEP)
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 humans, Sacubitril (AHU-377) (t max 0.5-1.1 h) are absorbed quickly. Sacubitril (AHU-377) 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).