MK-8245 is a liver-targeted inhibitor of stearoyl-CoA desaturase (SCD; IC50s = 3, 3, and 1 nM for rat, mouse, and human SCD1, respectively).1 It is selective for SCD1 over Δ5- and Δ6-desaturases (IC50s = >100,000 nM). MK-8245 (20-60 mg/kg) reduces the hepatic, but not Harderian gland, ratio of oleic acid to stearic acid, a marker of chronic SCD activity, and blood glucose levels, without inducing the formation of skin lesions or eye squinting behavior, in a mouse model of high-fat diet-induced obesity. It also inhibits hepatitis C virus (HCV) replication without inducing cytotoxicity in LucNeo2 cells (IC50 = 39.8 nM).2
1.Oballa, R.M., Belair, L., Black, W.C., et al.Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemiaJ. Med. Chem.54(14)5082-5096(2011) 2.Nio, Y., Hasegawa, H., Okamura, H., et al.Liver-specific mono-unsaturated fatty acid synthase-1 inhibitor for anti-hepatitis C treatmentAntiviral Res.132262-267(2016)