1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELXR-623Cat. No.: HY-10629CAS No.: 875787-07-8Synonyms: WAY 252623分式: CHClFN分量: 422.78作靶點: LXR作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 47 mg/mL (111.17 m

2、M)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.3653 mL 11.8265 mL 23.6530 mL5 mM 0.4731 mL 2.3653 mL 4.7306 mL10 mM 0.2365 mL 1.1826 mL 2.3653 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 LXR-623可以滲透腦屏障的 LXR 部分激動劑和 LXR 完全激動劑，IC5

3、0 分別為24 nM 和 179 nM。IC50 & Target IC50: 24 nM (LXR-), 179 nM (LXR-) 2 3體外研究LXR-623 potently kills U87EGFRvIII and GBM39 cells in vitro while completely sparing NHAs. LXR-623 also1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEincreases ABCA1 protein and decreases LDLR protein levels in all three ce

4、ll lines. LXR-623 suppressesLDLR expression, increases expression of the ABCA1 efflux transporter, and induces substantial cell deathin all of the GBM samples tested. LXR-623 (5 M) also induces GBM cell death through activation of LXR1. LXR-623 treatment of human PBMC in vitro significantly increase

5、s transcription of ABCA1 and ABCG14.體內(nèi)研究 LXR-623 (400 mg/kg, p.o.) crosses the blood-brain barrier, induces target gene expression, and achievestherapeutic levels in GBM cells in the brain with minimal activity in the periphery. LXR-623 inhibits tumorgrowth, promotes tumor cell death, and prolongs t

6、he survival of mice bearing intracranial patient-derivedGBMs 1. LXR-623 (1.5, 5 mg/kg/day) significantly reduces progression of atherosclerosis in animalscompared with the placebo group 2. WAY-252623 (15 and 50 mg/kg) results in a significant reduction ofatherosclerosis in a dose-dependent manner. W

7、AY-252623 (20, 60, and 120 mg/kg/day, p.o.) displaysneutral lipid effects in this CETP-expressing Syrian hamster 3. Moreover, LXR-623 (50 mg/kg) induces geneexpression in rodent peripheral blood cells in rat. LXR-623 (0, 15 and 50 mg/kg) dose-dependentlyupregulates transcription of ABCA1 and ABCG1 i

8、n monkey whole blood cells proportional to dose 4.PROTOCOLAnimal Five-week-old female athymic nu/nu mice are used in the experiment. A total of 1105 U87EGFRvIIIAdministration 1 IRFP720 or GBM39 IRFP720 cells in 5 L of PBS is intracranially injected into the mouse brain. Tumors areallowed to establis

9、h over the course of 7-10 days and engraftment of tumors is quantitatively confirmed viaFMT signal intensity. Tumor growth is monitored using an FMT 2500 fluorescence tomography system. Fordrug treatment studies, vehicle (0.5% methylcellulose, 2% Tween 80 in water) or LXR-623 (400 mg/kg)resuspended

10、in vehicle are administered to mice via oral gavage daily starting at day 7 postinjection.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Death Dis. 2019 May 28;10(6):416. Cell Death Dis. 2019 Mar 13;10(3):248.See more customer validati

11、ons on HYPERLINK / www.MedChemEREFERENCES1. Villa GR, et al. An LXR-Cholesterol Axis Creates a Metabolic Co-Dependency for Brain Cancers. Cancer Cell. 2016 Nov 14;30(5):683-693.2. Giannarelli C, et al. Synergistic effect of liver X receptor activation and simvastatin on plaque regression and stabili

12、zation: an magneticresonance imaging study in a model of advanced atherosclerosis. Eur Heart J. 2012 Jan;33(2):264-73.3. Quinet EM, et al. LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse. JLipid Res. 2009 Dec;50(12):2358-70.4. DiBlasio-Smith EA, et al. Discovery and implementation of transcriptional biomarkers of synthetic LXR agonists in peripheral blood cells.J Transl Med. 2008 Oct 16;6:59.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMcePdfHeigh