SR-18292 - PGC-1α 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESR-18292Cat. No.: HY-101491CAS No.: 2095432-55-4分式: CHNO分量: 366.5作靶点: PGC-1作通路: Metabolic Enzyme/Protease储存式: -80C, stored under nitrogen* 该产品在溶液状态不稳定，建议您现现配，即刻使。溶解性数据体外实验 DMSO : 100 mg/mL (272.85 mM)* means soluble, but saturat

2、ion unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.7285 mL 13.6426 mL 27.2851 mL5 mM 0.5457 mL 2.7285 mL 5.4570 mL10 mM 0.2729 mL 1.3643 mL 2.7285 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液；该产品在溶液状态不稳定，建议您现现配，即刻使。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储

3、备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.82 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.82 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (

4、6.82 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 SR-18292种 PPAR 共激活因-1 (PGC-1) 抑制剂，可促进 PGC-1 酰化，抑制糖异基因的表达，并减少肝细胞中葡萄糖的产。IC50 & Target PGC-1 1体外研究 The transcriptional coactivator PGC-1 plays a pivotal role in energy homeostasis by co-activatingtranscripti

5、on factors that regulate fat and glucose metabolism. SR-18292 increases the interaction of PGC-1with the acetyl transferase GCN5 and reduces co-activation of nuclear hormone receptor HNF4 by PGC-1.SR-18292 suppresses HNF4/PGC-1 gluconeogenic transcriptional function. By increasing the interactionof

6、GCN5 with PGC-1, SR-18292 increases the acetylation of specific PGC-1 lysine residues that mightsubsequently decrease its gluconeogenic activity 1.体内研究 SR-18292 reduces fasting blood glucose, increases hepatic insulin sensitivity and improves glucosehomeostasis in diabetic mice. The high fat diet (H

7、FD) fed mice, a dietary model of obesity and T2D, aretreated with SR-18292 (45mg/kg) via I.P. injection for 3 consecutive days and again on day 4 beforemeasuring fasting blood glucose. Strikingly, mice that are treated with SR-18292 have significantly lowerlevels of fasting blood glucose concentrati

8、ons compared to matched vehicle-treated control mice. Theinduction of gluconeogenic gene expression is a regulatory component of the response to fasting.Importantly, gluconeogenic gene expression, specifically that of Pck1, is inhibited in livers isolated from micetreated with SR-18292 1.PROTOCOLKin

9、ase Assay 1 For determination of GCN5 HAT activity U-2 OS cells overexpressing Ad-GCN5 are treated with SR-18292(10 M) for 18 h. Cells are lysed with buffer B (20 mM HEPES-KOH (pH 7.9), 125 mM NaCl, 1 mM EDTA, 1mM DTT, 1% IGEPAL (v/v), 10% glycerol (v/v), 5 mM NaF, 5 mM -glycerophosphate, 5 mM sodiu

10、m butyrateand 10 mM nicotinamide), supplemented with Protease Inhibitor Cocktail. FLAG-GCN5 isimmunoprecipitated with FLAG beads overnight at 4C following multiple washes with lysis buffer. GCN5 isthen eluted using 3 FLAG peptide and the purified protein is used to determine HAT activity using the H

11、ATInhibitor Screening Assay Kit 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 For cell viability determination using MTT, primary hepatocytes are seeded on a 96-well plate at 20,000cells/well. The following day cells are treated at diff

12、erent doses, as indicated, for 18 h treatment of primaryhepatocytes. 5 L of MTT reagent (5 mg/mL) is then added to each well (n=4/dose) and cells are incubatedfor 1h at 37C. Medium is discarded and dye is extracted by adding 100 L DMSO to each well. Forcytotoxicity determination using ToxiLight Non-

13、destructive Cytotoxicity Bioassay, hepatocytes are seeded ona 6-well plate and treated with either SR-18292 (20 M) or Cisplatin (50 M) for 18 h. 50 L of medium iscollected and used to measure cellular toxicity by adding 100 of adenylate kinase detection reagent andincubating 5 min at RT before measu

14、ring luminescence 1.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 For in vivo studies with DIO mice, males 6-8 weeks old are fed high fat diet (HFD) for the indicated time.

15、 Fordrug administration, SR-18292 (45 mg/kg) is injected via I.P. for 3 days between 4-5 pm and food is removedon day 3 at 5pm. The following morning (day 4) SR-18292 is injected again (for a total of 4 injections) andblood glucose is measured after 3 hours. Injection volume does not exceed 275 L pe

16、r mouse 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Cell Mol Neurobiol. 2019 Mar;39(2):265-286.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Sharabi K, et al. Selective Chemical Inhibition of PGC-1 Gluconeogenic Activity Ameliorates Type 2 Diab