GSK5182-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK5182Cat. No.: HY-111226CAS No.: 877387-37-6分式: CHNO分量: 417.54作靶点: Estrogen Receptor/ERR; Reactive Oxygen Species作通路: Others; Immunology/Inflammation; MetabolicEnzyme/Protease; NF-B储存式: Please store the product under the recom

2、mended conditions inthe COA.BIOLOGICAL ACTIVITY物活性 GSK5182种效选择性的 ERR 反向激动剂，其 IC50 值为 79 nM。GSK5182 不与其他核受体相互作，包括 ERR 和 ER，因为它在 ERR 的活性位点与 Y326 和 N346 具有额外的共价相互作。GSK5182还能增加肝癌细胞中 Reactive Oxyen Species (ROS) 的产。IC50 & Target ERR79 nM (IC50)体外研究GSK5182 (0-20 M; 0-hours; PLC/PRF/5 cells) treatment lead

3、s to a significant and dose-dependentreduction in the number of proliferating PLC/PRF/5 cells 1.GSK5182 (0-20 M; 24 hours; PLC/PRF/5 cells) treatment also causes a dose-dependent increase in theexpression of p21 and p27 while at the same time reducing the level of phosphorylated retinoblastomaprotei

4、n (p-pRb) 1.GSK5182 (10-20 M; PLC/PRF/5 cells) treatment induces cell cycle arrest at G1 phase, which in turninduces a corresponding dose-dependent reduction in the percentage of cells in S phase 1.Cell Proliferation Assay 1Cell Line: The human hepatoma cell line PLC/PRF/5Concentration: 0 M, 10 M, 2

5、0 MIncubation Time: 0 hour, 24 hours, 48 hours, 72 hours1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEResult: Led to a significant and dose-dependent reduction in the number of proliferatingPLC/PRF/5 cells.Western Blot Analysis 1Cell Line: The human hepatoma cell line PLC/PRF/5Concentration: 0 M,

6、 10 M, 20 MIncubation Time: 24 hoursResult: Caused a dose-dependent increase in the expression of p21 and p27 while at the sametime reducing the level of p-pRb.Cell Cycle Analysis 1Cell Line: The human hepatoma cell line PLC/PRF/5Concentration: 10 M, 20 MIncubation Time:Result: Induced cell cycle ar

7、rest.体内研究 GSK5182 (40 mg/kg; intraperitoneal injection; every day; 25 or 30 days; db/db mice, diet-induced obesitymice) specifically inhibits the transcriptional activity of ERR, and suppresses hepatic glucose productionthrough inhibition of hepatic gluconeogenesis. GSK5182 elicits anti-diabetic eff

8、ects in mouse models vianegative regulation of the hepatic gluconeogenesis program. GSK5182 normalizes hyperglycemia mainlythrough inhibition of hepatic glucose production 3.Animal Model: db/db mice (male, 7-12-week-old), diet-induced obesity (DIO) mice 3Dosage: 40 mg/kgAdministration: Intraperitone

9、al injection; every day; 30 days for db/db mice, 25 days for DIO miceResult: Inhibited the transcriptional activity of ERR, suppressed hepatic glucose productionthrough inhibition of hepatic gluconeogenesis.REFERENCES1. Kim JH, et al. Estrogen-related receptor is upregulated in liver cancer and its

10、inhibition suppresses livercancer cell proliferation viainduction of p21 and p27. Exp Mol Med. 2016 Mar 4;48:e213.2. Misra J, et al. ERR: a Junior Orphan with a Senior Role in Metabolism. Trends Endocrinol Metab. 2017 Apr;28(4):261-272.3. Kim DK, et al. Inverse agonist of nuclear receptor ERR mediates antidiabetic effect through inhibition of hepatic gluconeogenesis.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEDiabetes. 2013 Sep;62(9):3093-102.McePdfHeightCaution: Product has not been fu