Nicodicosapent 是一种脂肪酸烟酸共轭体，可以抑制固醇调节元件结合蛋白 (SREBP) 的活性，调节胆固醇代谢的蛋白质如 PCSK9，HMG-CoA reductase，ATP citrate lyase 和 NPC1L1 等的活性。
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.
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].
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].
[1]. Vu CB, et al. Synthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid. J Med Chem. 2016 Feb 11;59(3):1217-31.
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