| Identification | Back Directory | [Name]
GSK5182 | [CAS]
877387-37-6 | [Synonyms]
GSK5182
CS-2620
(E/Z)-GSK5182
(Z)-4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-5-hydroxy-2-phenylpent-1-en-1-yl)phenol
Benzenebutanol, δ-[[4-[2-(dimethylamino)ethoxy]phenyl](4-hydroxyphenyl)methylene]-, (δZ)- | [Molecular Formula]
C27H31NO3 | [MOL File]
877387-37-6.mol | [Molecular Weight]
417.55 |
| Chemical Properties | Back Directory | [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) | [form ]
Solid | [pka]
10.27±0.15(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [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]
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]. | Animal Model: | db/db mice (male, 7-12-week-old), diet-induced obesity (DIO) mice[3] | | Dosage: | 40 mg/kg | | Administration: | Intraperitoneal injection; every day; 30 days for db/db mice, 25 days for DIO mice | | Result: | Inhibited the transcriptional activity of ERRγ, suppressed hepatic glucose production through inhibition of hepatic gluconeogenesis.
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| [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 |
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