| 產(chǎn)品描述： | GW3965 HCl is an effective and specific LXR agonist for hLXRα/β (EC50: 190/30 nM). |
| 靶點(diǎn)： |
Liver X Receptor;LiverXReceptor |
| 體外研究： |
GW3965 recruits the steroid receptor coactivator 1 to human LXRα with EC50 of 125 nM in a cell-free ligand-sensing assay. GW3965 shows a potent antagonistic activity against hLXRα and hLXRβ in cell-based assays with EC50 of 190 nM and 30 nM, respectively. Besides, GW3965 also sows excellent selectivity over other nuclear receptors. In human islets, GW3965 (1 μM) reduces expression of selected pro-inflammatory cytokines including IL-8, monocyte chemotactic protein-1 and tissue factor. |
| 體內(nèi)研究： |
In mice, GW3965 at a dose of 10 mg/kg upregulates ABCA1 expression 8-fold and raises circulating levels of HDL by 30% with Cmax of 12.7 μg/mL and t1/2 of 2 hours. GW3965 (10 mg/kg) induces expression of ABCA1 and ABCG1 and shows potent antiatherogenic activity in both LDLR/and apoE/mice. In male sprague-dawley rats, GW3965 reduces Ang II-mediated increases in blood pressure and decreases vascular Ang II receptor gene expression. In Glioblastoma mouse model, GW3965 results in inducible degrader of LDLR-mediated LDLR degradation, increased expression of the ABCA1 cholesterol efflux transporter, and thus potently promotes tumor cell death. |
| 細(xì)胞實(shí)驗(yàn)： |
Cells are seeded in 96 wells and are treated after 24 hours with different drugs indicated in each experiment in medium containing 1% FBS or lipoprotein deficient serum. Relative proliferation is determined using Cell Proliferation 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, 37oC and the absorbance of the treated and untreated cells are measured using a microplate reader at 420 to 480 nm. Cells seeded in 12 well plates are counted using a hemocytometer, and dead cells are assessed using trypan blue exclusion assays. |
| 參考文獻(xiàn)： |
1. Guo D, et al. An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discov. 2011, 1(5), 442-456. 2. Joseph SB, et al. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci U S A. 2002, 99(11), 7604-7609. 3. Collins JL, et al. Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J Med Chem. 2002, 45(10), 1963-1966. 4. Scholz H, et al. The synthetic liver X receptor agonist GW3965 reduces tissue factor production and inflammatory responses in human islets in vitro. Diabetologia. 2009, 52(7), 1352-1362. 5. Leik CE, et al. GW3965, a synthetic liver X receptor (LXR) agonist, reduces angiotensin II-mediated pressor responses in Sprague-Dawley rats. Br J Pharmacol. 2007, 151(4), 450-456. |
| 溶解性： |
Soluble in DMSO、Ethanol |
| 保存條件： |
-20°C |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.617 ml |
8.084 ml |
16.168 ml |
| 5 mM |
0.323 ml |
1.617 ml |
3.234 ml |
| 10 mM |
0.162 ml |
0.808 ml |
1.617 ml |
| 50 mM |
0.032 ml |
0.162 ml |
0.323 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
上海工商
危險(xiǎn)品化學(xué)品經(jīng)營許可證（不帶存儲）
營業(yè)執(zhí)照(三證合一)
北京