ETC-1002

A small molecule regulator of lipid and carbohydrate metabolism that targets ACC (acetyl-CoA carboxylase) with IC50 of 29 uM without activating the AMPK pathway in vitro; reduces circulating proatherogenic lipoproteins, hepatic lipids, and body weight in a hamster model of hyperlipidemia.Diabetes Phase 2 Clinical (In Vitro) :Bempedoic acid (ETC-1002) activates AMP-activated protein kinase in a Ca2+/calmodulin-dependent kinase β-independent and liver kinase β 1-dependent manner, without detectable changes in adenylate energy charge. Bempedoic acid is shown to rapidly form a CoA thioester in liver, which directly inhibits ATP-citrate lyase. In cells treated with Bempedoic acid (ETC-1002), increased levels of AMP-activated protein kinase (AMPK) phosphorylation coincide with reduced activity of MAP kinases and decreased production of proinflammatory cytokines and chemokines. (In Vivo) :A marked and sustained increase in AMPK and ACC phosphorylation is found in rat livers following two weeks of treatment with Bempedoic acid (ETC-1002) . Bempedoic acid is >100-fold more prevalent than the CoA thioester in rat liver and is associated with AMPK activation. Bempedoic acid (ETC-1002) suppresses thioglycollate-induced homing of leukocytes into mouse peritoneal cavity. In a mouse model of diet-induced obesity, Bempedoic acid restores adipose AMPK activity, reduces JNK phosphorylation, and diminishes expression of macrophage-specific marker 4F/80.