GW9662 - PPAR Antagonist - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGW9662Cat. No.: HY-16578CAS No.: 22978-25-2分式: CHClNO分量: 276.68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 : 100 mg/mL (361.43 mM)H2O : 40% PEG300 5% Tw

2、een-80 45% salineSolubility: 2.5 mg/mL (9.04 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (9.04 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 GW9662有效，选择性的 PPAR 拮抗剂，IC50值为3.3 nM，PPAR和PPAR的选择性10倍和1000倍。IC50 & Target PPAR PPAR

3、 PPAR3.3 nM (IC50) 32 nM (IC50) 2000 nM (IC50)体外研究 GW9662 inhibits radioligand binding to PPAR, PPAR, and PPAR with pIC50s of 8.480.27 (IC50=3.3 nM;n=10), 7.490.17 (IC50=32 nM; n=9), and 5.690.17 (IC50=2000 nM; n=3), respectively. GW9662 hasnanomolar IC50 versus PPAR and is 10- and 600-fold less pot

4、ent in binding experiments using PPAR andPPAR, respectively. In cell-based reporter assays, GW9662 is a potent and selective antagonist of full-length PPAR 1. Co-treatment with both 50 M Rosiglitazone and 10 M GW9662 results in statisticallylower viable cell numbers after 7 days when compared to tre

5、atment with either 50 M rosiglitazone (P=0.001)or 10 M GW9662 (P=0.01) alone 2.体内研究 Bone marrow (BM) nucleated cell counts in both BADGE- and GW9662(1 mg/kg, i.p.)-treated mice aresignificantly higher than counts in the aplastic anemia (AA) group 3. GW9662 (1 mg/kg, i.p.) largelyattenuates the renop

6、rotective effects of Lipopolysaccharide (LPS) in the rat 4.PROTOCOLCell Assay 2 Cells (MCF7, MDA-MB-231, MDA-MB-468) are plated in 96-well plates at a density of 1103 cells per well inRPMI medium. After overnight incubation to allow for cell attachment, the medium is removed and replacedwith fresh m

7、edium containing varying concentrations of Rosiglitazone (1-100 M), GW9662 (100 nM-50 M)or solvent (DMSO) alone. MDA-MB-231 cells are also subjected to combinations of Rosiglitazone (10, 50 M) and GW9662 (1, 10 M) added simultaneously. The final concentration of DMSO in all cases does notexceed 0.1%

8、 and is not found to be cytotoxic in any of the cell lines tested at this concentration.Chemosensitivity is assessed following a continuous 72 h exposure using a standard MTT assay.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administrat

9、ion 34 Inbred C57BL/6 (B6, H2b/b), DBA/1J (DBA/1, H2q/q), FVB/NJ (FVB, H2q/q) mice and congenic C.B10-H2b/b/LilMcd (CB10, H2b/b) mice are used. BADGE or GW9662, are administrated by daily intraperitonealinjection at 30 mg/kg for BADGE, or at 1 mg/kg for GW9662, from one day prior to the experiment a

10、ndcontinued for up to 2 weeks. In the FVB AA model, some mice are injected with cyclosporine A (CsA, 50mg/kg/day) starting 1 hour after the LN injection, and continued for 5 days as immunosuppression. At the endof the experiments, the mice are euthanized by CO2 inhalation.Rats 4Sixty-two male Wistar

11、 rats weighing 215 to 315 g are used in this study. Animals are randomly allocated into6 groups as follows: (1) I/R group: control, rats are administered 10% (v/v) DMSO (vehicle for GW9662, 1 mL/kg, IP) 24 and 12 hours prior to renal I/R, and saline (vehicle for LPS, 1 mL /kg, IP) 24 hours prior to

12、renal2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEI/R (N=12); (2) I/R LPS group: rats are administered 10% (v/v) DMSO (vehicle for GW9662, 1 mL /kg, IP) 24and 12 hours prior to renal I/R, and LPS (1 mg/kg, IP) 24 hours prior to renal I/R (N=11); (3) I/R GW9662group: rats are administered GW9662

13、(1 mg/kg, IP) 24 and 12 hours prior to renal I/R, and saline (vehicle forLPS, 1 mL /kg, IP) 24 hours prior to renal I/R (N=9); (4) I/R LPS+GW9662 group: rats are administeredGW9662 (1 mg/kg, IP) 24 and 12 hours prior to renal I/R, and LPS (1 mg/kg, IP) 24 hours prior to renal I/R(N=11); (5) Sham gro

14、up: rats are subjected to the same surgical procedures as above, except for renal I/R.Rats are administered 10% (v/v) DMSO (vehicle for GW9662, 1 mL /kg, IP) and saline (vehicle for LPS, 1 mL/kg, IP) at times equivalent to those described above (N=12); (6) Sham GW9662 group: rats are subjected tothe

15、 same surgical procedures as above, except for renal I/R. Rats are administered GW9662 (1 mg/kg, IP)and saline (vehicle for LPS, 1 mL /kg, IP) at times equivalent to those described above (N=7).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

16、 Cell Death Differ. 2019 Feb 11. Br J Pharmacol. 2018 Aug;175(16):3379-3393. PLoS Pathog. 2016 Aug 24;12(8):e1005823. J Mol Cell Cardiol. 2019 Mar;128:160-178. Front Pharmacol. 2017 Jul 7;8:445.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Leesnitzer LM, et al. Functional con

17、sequences of cysteine modification in the ligand binding sites of peroxisome proliferator activatedreceptors by GW9662. Biochemistry. 2002 May 28;41(21):6640-50.2. Seargent JM, et al. GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumour cells and promotes the anticancereffects

18、of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation. Br J Pharmacol. 2004 Dec;143(8):933-7.3. Sato K, et al. PPAR antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function.Haematologica.2016 Jan;101(1):57-67.4. Collino M, et al. The selective PPARgamma antagonist GW9662 reverses the protection of LPS i