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AHU-377 hemicalcium salt

Cat. No. M6173
AHU-377 hemicalcium salt Structure
Synonym:

Sacubitril hemicalcium salt

Size Price Availability Quantity
10mg USD 180 In stock
50mg USD 600 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

In vitro: LCZ696 is a single molecule that is comprised of molecular moieties of valsartan, an ARB, and AHU377, a neprilysin inhibitor (1:1 ratio). AHU377 is converted by enzymatic cleavage of the ethyl ester into the active neprilysin inhibiting metabolite LBQ657. The inactive NEPi precursor, AHU377, 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 humans, AHU377 (tmax 0.5-1.1 h) are absorbed quickly. AHU377 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 AHU377. Urinary volume is also potentiated in animals which receive an iv administration of AHU377.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 430.52
Formula C24H28Ca0.5NO5
CAS Number 1369773-39-6
Purity >98%
Solubility 54 mg/mL in DMSO
Storage at -20°C
References

Pharmacokinetic, pharmacodynamic, and antihypertensive effects of the neprilysin inhibitor LCZ-696: sacubitril/valsartan.
Chrysant SG, et al. J Am Soc Hypertens. 2017 Jul;11(7):461-468. PMID: 28652105.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: AHU-377 hemicalcium salt, Sacubitril hemicalcium salt supplier, inhibitors

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