Nicodicosapent

Nicodicosapent is a fatty acid niacin conjugate that is also an inhibitor of the sterol regulatory element binding protein (SREBP), a key regulator of cholesterol metabolism proteins such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1. In Vitro: Nicodicosapent decreases the production of mature SREBP-2 protein in HepG2 cells, but does not interact with the GPR109A receptor. Nicodicosapent shows a synergistic inhibition on secreted PCSK9 and has an IC₅₀ value of 17 μM. Nicodicosapent significantly inhibits ApoB secretion in a dose-dependent manner with IC₅₀ of 27 μM. Nicodicosapent results in a time-dependent hydrolysis in HepG2 cells^[1]. In Vivo: Nicodicosapent (100 mg/kg po) produces high plasma levels of nicotinuric acid in the plasma. ApoE*3-Leiden mice treated with Nicodicosapent show a significant reduction in PCSK9 levels, LDL particles including VLDL and LDL cholesterol, as well as plasma triglycerides^[1].