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MK-8245 is a highly potent liver-targeted stearoyl-CoA desaturase (SCD) inhibitor with an IC50 of 1 nM for human SCD1 enzyme. MK-8245 inhibits the SCD enzyme solely in the liver and not in other tissues for the following reasons. When SCD inhibition has been measured by desaturation index in tissues of rodents treated with MK-8245, the desaturation index is significantly decreased in liver but not in other tissues such as skin, eye and adipose tissue. MK-8245 is distributed primarily to the liver, with low exposure in tissues associated with potential adverse events. MK-8245 is significantly shifted in the non-OATP HepG2 cellular assay. MK-8245 should possess the desired lack of cell penetration. MK-8245 ameliorates glucose clearance dose-dependently to a similar extent with an ED50 of 7 mg/kg.
| Cell Experiment | |
|---|---|
| Cell lines | |
| Preparation method | |
| Concentrations | |
| Incubation time | |
| Animal Experiment | |
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| Animal models | Male C57/Bl6 mice |
| Formulation | Suspended in 1% methocel in saline |
| Dosages | ~30 mg/kg |
| Administration | Orally |
| Molecular Weight | 467.25 |
| Formula | C17H16BrFN6O4 |
| CAS Number | 1030612-90-8 |
| Solubility (25°C) | DMSO 90 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[1] Takayuki Hishiki, et al. Stearoyl-CoA desaturase-1 is required for flavivirus RNA replication
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