MK-8245

MK-8245 is a potent, selective liver-targeted stearoyl-CoA desaturase (SCD) inhibitor with IC50 of 3, 3 and 1 nM for rat, mouse and human SCD1 enzyme, respectively; displays highly selective over the Δ-5 and Δ-6 desaturases (IC50>100 uM) ; has IC50 values of 68 nM and 1066 nM in Hum HepG2 and rat hepatocyte assays, demonstrates HepG2/hepatocyte ratio of 16:1; exhibits preclinical antidiabetic and antidyslipidemic efficacy in vivo, demonstrats maximal liver SCD inhibition while sparing inhibition in the skin and eye tissues associated with adverse events.Diabetes Phase 1 Discontinued (In Vitro) :MK-8245 is a potent and liver-specific SCD inhibitor.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.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. (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.MK-8245 improves glucose clearance in a dose-dependent manner in eDIO mice administrated before the glucose challenge.