Icosabutate

Icosabutate is an orally active engineered fatty acid and a dual FFAR1/FFAR4 (GPR40/GPR120) agonist with EC₅₀ values of 10 μM and 15.5 μM, respectively. Icosabutate acts as a partial agonist of PPAR-α, with an EC₅₀ of 208 nM. Icosabutate inhibits the arachidonic acid cascade and exhibits antioxidant and anti-apoptotic activities. Icosabutate can be used in the research of nonalcoholic steatohepatitis, metabolic dysfunction-associated steatohepatitis, and atherosclerosis^[1][2][3][4]. IC50 & Target:IC50: non-HDL-C^[2] In Vitro:Icosabutate fully activates the human FFAR4 β-arrestin2 pathway in a transfected cell line with an EC₅₀ of 15 μM^[4].
Icosabutate activates the human FFAR1 calcium flux pathway in transfected HEK293 cells with an EC₅₀ of 10 μM and 90% maximum efficacy^[4].
Icosabutate partially activates human PPAR-α in transfected HEK293 cells with an EC₅₀ of 208 nM and 62% maximum efficacy^[4].
Icosabutate significantly inhibits proliferation of LX-2 myofibroblasts^[4]. In Vivo:Icosabutate (135 mg/kg; p.o.; once daily; for 5 consecutive weeks) improves glucose metabolism and insulin sensitivity in male ob/ob mice, reducing HOMA-IR by 87% and plasma alanine transaminase levels by 33%^[1].
Icosabutate (112 mg/kg; p.o.; once daily; for 20 weeks) reduces microvesicular steatosis, hepatic inflammation, fibrosis, lipotoxic lipid species, and oxidative stress in atherosclerotic model mice^[1].
Icosabutate (45-135 mg/kg; p.o.; once daily; 4-8 weeks) dose-dependently attenuates hepatic steatosis, inflammation, oxidative stress, apoptosis and progressive fibrosis in established non-alcoholic steatohepatitis (NASH) of male ob/ob mice^[3].
Icosabutate (112 mg/kg; p.o.; once daily; for 4 consecutive weeks) reduces plasma TAG and total cholesterol by 70% and 68%, respectively, in hyperlipidemic mice by enhancing hepatic VLDL remnant clearance and LDL-R-mediated cholesterol uptake^[3].
Icosabutate (37.5 mg/kg; p.o.; once daily; 4.5 weeks, followed by 15 mg/kg; p.o.; once daily; 12.5 weeks) reduces total cholesterol exposure in mice by approximately 29%, and decreases the formation, severity and number of atherosclerotic lesions^[3].
Administration of icosabutate (135 mg/kg; once daily; for 4 weeks) for 4 weeks significantly improves glycemic control and reduces plasma triglyceride, cholesterol and AST levels in obese Zucker rats^[4].