L-165041 _PPAR Agonist - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEL-165041Cat. No.: HY-20019CAS No.: 79558-09-1分式: CHO分量: 402.44作靶點(diǎn): PPAR作通路: Cell Cycle/DNA Damage儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (124.24 mM; Need ultrasonic)H2O : 4

2、0% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.21 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.21 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 L-165041種細(xì)胞滲透的 PPAR 激動(dòng)劑，對(duì) PPAR 和 PPAR 的 Ki 值分別為 6 nM 和 約 730 nM，可以在

3、 NIH-PPAR 細(xì)胞中誘導(dǎo)脂肪細(xì)胞分化。IC50 & Target PPAR PPAR6 nM (Ki) 730 nM (Ki)體外研究 L-165041 is a PPAR agonist, with Kis of 6 nM and appr 730 nM for PPAR and PPAR, respectively 1. L-165041 (1 or 5M) inhibits VEGF-induced endothelial cells (ECs) proliferation and migration. L-165041negatively affects cell cycle p

4、rogression in VEGF-activated human umbilical vein ECs (HUVECs). L-165041(10M)inhibits PPAR-independent, VEGF-induced angiogenesis 2. PPAR ligand L-165041 inhibitsPDGF-induced rVSMC proliferation and migration. With 1 h of L-165041 pretreatment, PDGF-inducedcellular migration is inhibited. L-165041 (

5、10 M) significantly suppresses S phase transition induced byPDGF 4.體內(nèi)研究 L-165041 (5 mg/kg/day, i.p.) significantly lowers the formation of lipid droplets in mice. L-165041 markedlyreduces the level of both the hepatic cholesterol and triglycerides in mice. L-165041 increases mRNAexpression levels of

6、 PPAR compared to the vehicle group. Lipoprotein lipase (LPL) expression in L-165041-treated mice is significantly higher than that in the vehicle group 3.PROTOCOLCell Assay 2 Human umbilical vein ECs (HUVECs) are cultured in EGM-2. Subconfluent HUVECs are made quiescent byserum starvation EBM-2 con

7、taining 0.1% fetal bovine serum (FBS) for 4h. The cells are pretreated with thePPAR ligand L-165041 or GW501516 for 6h followed by VEGF (10ng/mL) induction 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal LDLR/ mice are divided into vehicle (0.1

8、 N NaOH) and L-165041 (5 mg/kg/day) group (9 animals in eachAdministration 3 group). LDLR/ mice receive either NaOH or L-165041 via daily intraperitoneal injection (i.p.) for 16 weekswith the Western diet. Body weight is measured once a week and the blood samples for a serum parameteranalysis are co

9、llected using an eye-bleeding method every 4 weeks. At the end of the experiment, LDLR/mice are fasted for 24 h before sacrificed and the liver samples are either fixed in formalin or frozen at 70Cfor further analysis. All animals are housed in polycarbonate cages in a room with a 12-h light/12-h da

10、rkcycle, and maintained at a constant temperature of 22C 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Berger J, et al. Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biologicaleffec

11、ts. J Biol Chem. 1999 Mar 5;274(10):6718-25.2. Park, Jin-Hee., et al. The PPAR ligand L-165041 inhibits vegf-induced angiogenesis, but the antiangiogenic effect is not related toPPAR. Journal of Cellular Biochemistry (2012), 113(6), 1947-1954.3. Lim, Hyun-Joung., et al. PPAR ligand L-165041 ameliora

12、tes Western diet-induced hepatic lipid accumulation and inflammation in2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemELDLR-/- mice. European Journal of Pharmacology (2009), 622(1-3), 45-51.4. Lim, Hyun-Joung., et al. PPAR agonist L-165041 inhibits rat vascular smooth muscle cell proliferation and migration via inhibition of cellcycle. Atherosclerosis (Amsterdam, Netherlands) (2009), 202(2), 446-454.McePdfHeightCauti