GSK5182

GSK5182 is a highly selective and orally active inverse agonist of estrogen-related receptor γ (ERRγ) with an IC₅₀ of 79 nM. GSK5182 does not interact with other nuclear receptors, including ERRα or ERα. GSK5182 also induces reactive oxyen species (ROS) generation in hepatocellular carcinoma (HCC)^[1][2][3]. In Vitro: GSK5182 (0-20 μM; 0-hours; PLC/PRF/5 cells) treatment leads to a significant and dose-dependent reduction in the number of proliferating PLC/PRF/5 cells^[1].
GSK5182 (0-20 μM; 24 hours; PLC/PRF/5 cells) treatment also causes a dose-dependent increase in the expression of p21 and p27 while at the same time reducing the level of phosphorylated retinoblastoma protein (p-pRb)^[1].
GSK5182 (10-20 μM; PLC/PRF/5 cells) treatment induces cell cycle arrest at G1 phase, which in turn induces a corresponding dose-dependent reduction in the percentage of cells in S phase^[1]. In Vivo: GSK5182 (40 mg/kg; intraperitoneal injection; every day; 25 or 30 days; db/db mice, diet-induced obesity mice) specifically inhibits the transcriptional activity of ERRγ, and suppresses hepatic glucose production through inhibition of hepatic gluconeogenesis. GSK5182 elicits anti-diabetic effects in mouse models via negative regulation of the hepatic gluconeogenesis program. GSK5182 normalizes hyperglycemia mainly through inhibition of hepatic glucose production^[3].