MK-8245

MK-8245 is a potent, liver-targeted stearoyl-CoA desaturase (SCD) inhibitor, with IC₅₀s of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1, with antidiabetic and antidyslipidemic efficacy^[1]. IC50 & Target: IC50: 1 nM (human SCD1), 3 nM (rat SCD1), 3 nM (mouse SCD1)^[1] In Vitro: MK-8245 is a potent and liver-specific SCD inhibitor^[1].
MK-8245 displays similar potencies against human, rat and mouse SCD1, with IC₅₀ values of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1^[1].
MK-8245 exhibits a significant SCD inhibition in the rat hepatocyte assay which contains functional, actives organic anion transporting polypeptides (OATPs) with IC₅₀ of 68 nM, while being only weakly active OATPs in the HepG2 cell assay which is devoid of active with IC₅₀ of ~1 μM^[1].
In Vivo: MK-8245 (10mg/kg; p.o.) exhibits a tissue distribution profile concentrated in the liver, with low exposure in tissues associated with potential adverse events in rats, dogs, and rhesus monkeys^[1].
MK-8245 improves glucose clearance in a dose-dependent manner in eDIO mice administrated before the glucose challenge^[1].