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.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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.
|Solubility||54 mg/mL in DMSO|
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.
Photochlor is a lipophilic, second-generation, chlorin-based photosensitizer.
AMPPD is a new biochemistry ultrasensitive alkaline phosphatase substrate.
DM1-SMCC is DM1 with a reactive linker SMCC, which can react with antibody to make ADC.
Mitapivat is a potent human R-type pyruvate kinase (PKR) inhibitor.
VH-298 is a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, with a Kd value of 80 to 90 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.