GSK5182 Chemical Properties

Boiling point:

567.6±50.0 °C(Predicted)

Density 

1.132±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO:54.5(Max Conc. mg/mL);130.52(Max Conc. mM)
Ethanol:84.0(Max Conc. mg/mL);201.17(Max Conc. mM)

pka

10.27±0.15(Predicted)

form 

Solid

color 

Off-white to light yellow

GSK5182 Usage And Synthesis

Uses

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].

Biological Activity

GSK5182 is an orally available 4-hydroxy-tamoxifen (4-OHT) analog and a high affinity estrogen receptor-related receptor γ (ERRγ) inverse agonist (68% inhibition at 1 μM by reporter assay) with 25-fold reduced affinity and little antagonistic activity toward ERRα (No inhibition against 100 nM estradiol-induced reporter activity up to 1 μM). GSK5182 effectively inhibits ERRγ-dependent gene expression and biological functions both in cultures (1-10 μM) and in various animal studies in vivo (10-80 mg/kg i.p. or p.o. in rats and mice).

in vivo

IC 50

ERRγ: 79 nM (IC₅₀); Reactive Oxygen Species

References

[1] Kim JH, et al. Estrogen-related receptor γ is upregulated in liver cancer and its inhibition suppresses livercancer cell proliferation via induction of p21 and p27. Exp Mol Med. 2016 Mar 4;48:e213. DOI:10.1038/emm.2015.115
[2] Misra J, et al. ERRγ: a Junior Orphan with a Senior Role in Metabolism. Trends Endocrinol Metab. 2017 Apr;28(4):261-272. DOI:10.1016/j.tem.2016.12.005
[3] Kim DK, et al. Inverse agonist of nuclear receptor ERRγ mediates antidiabetic effect through inhibition of hepatic gluconeogenesis. Diabetes. 2013 Sep;62(9):3093-102. DOI:10.2337/db12-0946