Eliglustat

Cell experiment:

The inhibitory activity of Genz-112638 is determined indirectly by measuring its effect on the cell surface levels of the gangliosides GM1 and GM3 on either K562 or B16/F10 cells. GM1 levels on the K562 cells are determined by incubating the cells with increasing amounts of Genz-112638 (0.6-1000 nM) for 72 h after which the cells are harvested and stained using 10 μg of recombinant cholera toxin-FITC in 100 μL phosphate buffered saline (PBS) containing 0.5% bovine serum albumin (BSA) for 30 min on ice. Cells are ished, resuspended in PBS containing 0.5% BSA and the fluorescence quantitated[1].

Animal experiment:

Mice: Eliglustat hemitartrate is dissolved in water for injection and administered in a dose escalation from 75 mg/kg/day to 150 mg/kg/day over the course of nine days, with three days at each dose and increments of 25 mg/kg/day. Mice are weighed three times per week to monitor the potential impact of the drug on their overall health. Animals are killed by carbon dioxide inhalation[1].

References:

[1]. McEachern KA, et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy ofGaucher disease. Mol Genet Metab. 2007 Jul;91(3):259-68.