GSK3787 - PPAR Antagonist - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK3787Cat. No.: HY-15577CAS No.: 188591-46-0分式: CHClFNOS分量: 392.78作靶点: PPAR作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (127.30 mM)H2O : 40% PEG300 5%

2、 Tween-80 45% salineSolubility: 2.5 mg/mL (6.36 mM); Suspended solution; Need ultrasonic2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.36 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 GSK3787种选择性和不可逆的过氧化物酶体增殖物激活受体 (PPAR) 拮抗剂，pIC50 为 6.6。IC50

3、& Target PPAR6.6 nM (pIC50)体外研究 GSK3787 is identified as a potent and selective hPPAR ligand (pIC50=6.6) with no measurable affinity forhPPAR or hPPAR (pIC50 5) in our standard in vitro ligand displacement assay. GSK3787 is inactiveagainst hPPAR and hPPAR in similar functional antagonist assays. GSK

4、3787 fails to activate the receptorin a standard hPPAR-GAL4 chimera cell-based reporter assay. GSK3787 is a selective PPAR antagonistwith equipotent species activity against the human and mouse receptor 1.体内研究 GSK3787 has pharmacokinetic properties suitable for use as an in vivo PPAR antagonist tool

5、 compound inmice. GSK3787 is administered intravenously (0.5 mg/kg) and orally (10 mg/kg) to male C57BL/6 mice.Mean clearance (CL) and volume of distribution at steady state (Vss) following iv administration are 3911(mL/min)/kg and 1.70.4 L/kg, respectively. Following oral administration, good expos

6、ure (Cmax=881166ng/mL, AUCinf=3343332 hng/mL), half-life (2.71.1 h), and bioavailability (F=7717%) are observed 1.Oral administration of GSK3787 (10 mg/kg) leads to a serum Cmax of 2.20.4 M in C57BL/6 male mice.Oral administration of GW0742 causes an increase in expression of Angptl4 and Adrp mRNA (

7、known PPAR/ target genes) in wild-type mouse colon epithelium, and this effect is not found in Ppar/-null mousecolon epithelium. Coadministration of GSK3787 with GW0742 effectively prevents the ligand-inducedexpression of both Angptl4 and Adrp mRNA in wild-type mouse colon epithelium, and this effec

8、t is not foundin Ppar/-null mouse colon epithelium. Oral administration of GSK3787 causes a modest increase inpromoter occupancy of PPAR/ in the PPRE region of both the Angptl4 and Adrp genes, butcoadministration of GSK3787 with GW0742 results in markedly less accumulation of PPAR/ in the PPREregion

9、 of both the Angptl4 and Adrp genes in wild-type mouse colon epithelium 2.PROTOCOLAnimal Mice 2Administration 2 For RNA and DNA analysis, male wild-type and Ppar/-null mice are administered vehicle (corn oil),GW0742 (10 mg/kg), GSK3787 (10 mg/kg), or GW0742 and GSK3787 by oral gavage 3 h before euth

10、anasia.After euthanasia, colons are carefully dissected. To isolate colon epithelium, colons are flushed withphosphate-buffered saline, and epithelial cells are scraped from mucosa using a razor blade. The isolatedtissues are used for RNA isolation. For glucose-tolerance tests, male wild-type and Pp

11、ar/-null mice areadministered vehicle (corn oil), GW0742 (10 mg/kg), GSK3787 (10 mg/kg), or Rosiglitazone (20 mg/kg) byoral gavage once a day for 2 weeks.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2/3 Master of Small Molecules 您边的抑制剂师www

12、.MedChemE Oncol Res. 2019 Apr 8. Front Pharmacol. 2018 Jun 28;9:648. Nutrition. 2019 Apr;60:217-226.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Shearer BG, et al. Identification and characterization of 4-chloro-N-(2-5-trifluoromethyl)-2-pyridylsulfonylethyl)benzamide (GSK37

13、87),a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist. J Med Chem. 2010 Feb 25;53(4):1857-61.2. Palkar PS, et al. Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-beta/delta antagonistGSK3787. Mol Pharmacol. 2010 Sep;78(3):419-30.McePdf