GW3965-hydrochloride - LXR Agonist - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGW3965 hydrochlorideCat. No.: HY-10627ACAS No.: 405911-17-3分式: CHClFNO分量: 618.51作靶點(diǎn): LXR作通路: Metabolic Enzyme/Protease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 : 125 mg/mL (202.10 mM)H2

2、O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.04 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.04 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5

3、 mg/mL (4.04 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 GW3965 hydrochloride是肝 X 受體(LXR) 的激動(dòng)劑，抑制 hLXR 和 hLXR 的 EC50 分別為 190 和 30 nM。IC50 & Target EC50: 190 nM (hLXR), 30 nM (hLXR) 4體外研究 GW3965 hydrochloride promotes GBM cell death in vitro with enhanced efficacy in EGFRvIII-expressingtumor cells. GW3

4、965 hydrochloride up-regulates expression of the cholesterol transporter gene ABCA1 andthe E3 ubiquitin ligase IDOL and reduces LDLR levels 2. LXR ligands inhibits platelet aggregation andcalcium mobilization stimulated by collagen or CRP. GW3965 hydrochloride (1 or 5 M) displays a minorinhibitory e

5、ffect on fibrinogen binding and P-selectin exposure, when platelets are stimulated with 1 g/mLCRP. But using higher concentrations of GW3965 hydrochloride (10 M) or T0901317 (40 M), the levels offibrinogen and P-selectin on the platelet surface are reduced 3.體內(nèi)研究 GW3965 hydrochloride induces an incr

6、ease of neuroactive steroids in the spinal cord, the cerebellum and thecerebral cortex of STZ-rats, but not in the CNS of non-pathological animals. GW3965 hydrochloridetreatment induces an increase of dihydroprogesterone in the spinal cord of diabetic animals in associationwith an increase of myelin

7、 basic protein expression 1. GW3965 hydrochloride (40 mg/kg, p.o.) stronglyinduces ABCA1 expression and reduces LDLR expression, and this is accompanied by 59% inhibition oftumor growth, and a 25-fold increase in GBM cell apoptosis in vivo 2. GW3965 hydrochloride (2 mg/kg, i.v.)increases bleeding ti

8、me and modulated platelet thrombus formation in vivo 3.PROTOCOLCell Assay 2 Cells are seeded in 96 wells and are treated after 24 hours with different drugs indicated in each experimentin medium containing 1% FBS or lipoprotein deficient serum. Relative proliferation is determined using CellProlifer

9、ation Assay Kit. Cells are incubated 1.5 hrs after adding tetrazolium salt WST-1 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfo-phenyl)-2H-tetrazolium, monosodium salt at 5% CO2, 37C and theabsorbance of the treated and untreated cells are measured using a microplate reader at 420 to 480 nm.Cell

10、s seeded in 12 well plates are counted using a hemocytometer, and dead cells are assessed usingtrypan blue exclusion assays.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Diabetes is induced in two-month-old male rats by a single i.p. injection

11、of freshly prepared STZ (65 mg/kg) inAdministration 1 0.09 M citrate buffer, pH 4.8. Control animals are injected with 0.09 mol/L citrate buffer at pH 4.8.Hyperglycemia is confirmed 48 h after streptozotocin injection by measuring tail vein blood glucose levelsusing a glucometer OneTouch Ultra2. Onl

12、y animals with mean plasma glucose levels over 300 mg/mL areclassified as diabetic. Glycemia is also assessed before treatment with Ro5-4864 or GW3965 hydrochlorideand before death. Two months after STZ injection, diabetic animals are treated once a week with Ro5-48642/3 Master of Small Molecules 您邊

13、的抑制劑師www.MedChemE(3 mg/kg) or GW3965 hydrochloride (50 mg/kg). Thus, they receive four subcutaneous injections in a month.Control diabetic rats receive 200 L of vehicle (sesame oil). Four-month-old non-diabetic male rats areinjected, following the same experimental schedule, with Ro5-4864, GW3965 hy

14、drochloride or vehicle. Ratsare killed 24 h after the last treatment.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) Bioconjug Chem. 2015 Nov 18;26(11):2216-22. Am J Physiol Endocrinol Metab. 2019 Jun 1;316(6):E1136-E1145.See more customer v

15、alidations on HYPERLINK / www.MedChemEREFERENCES1. Mitro, Nico., et al. LXR and TSPO as new therapeutic targets to increase the levels of neuroactive steroids in the central nervous systemof diabetic animals. Neurochemistry International (2012), 60(6), 616-621.2. Guo, Deliang., et al. An LXR Agonist

16、 Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR-DependentPathway. Cancer Discovery (2011), 1(5), 442-456.3. Spyridon, Michael., et al. LXR as a novel antithrombotic target. Blood (2011), 117(21), 5751-5761.4. Collins JL, et al. Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary