Resatorvid-TAK-242-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEResatorvidCat. No.: HY-11109CAS No.: 243984-11-4Synonyms: TAK-242; CLI-095分式: CHClFNOS分量: 361.82作靶点: Toll-like Receptor (TLR); Autophagy作通路: Immunology/Inflammation; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 m

2、onths-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (276.38 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.75 mg/mL (7.60 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.75 mg/mL (7.60 mM); Suspended solution; Need ultrasonic1/3 Master of Small Mol

3、ecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.75 mg/mL (7.60 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Resatorvid (TAK-242)种有效的 TLR4 信号传导抑制剂，可选择性地抑制TLR-介导的细胞因和氧化氮的产。IC50 & Target TLR4 1体外研究 In RAW264.7 cells and mouse peritoneal macrophages, Resatorvid (TAK-242) suppress

4、eslipopolysaccharide (LPS)-induced production of NO, tumor necrosis factor- (TNF-), and interleukin (IL)-6,with IC50 of 1.1 to 11 nM. Resatorvid (TAK-242) also suppresses the production of these cytokines fromLPS-stimulated human peripheral blood mononuclear cells (PBMCs) at IC50 values from 11 to 3

5、3 nM 1.体内研究 Resatorvid (TAK-242) apparently reduces the serum anti-dsDNA levels in both genotype mice. Alternatively,IFN-, TNF-, and IL-1 production is markedly inhibited by Resatorvid (TAK-242), but their concentrationsare still greatly higher than those in NS-treated counterparts 2. Resatorvid (TA

6、K-242) pre-stressadministration prevents the accumulation of potentially deleterious inflammatory and oxidative/nitrosativemediators in the brain frontal cortex of rats. Resatorvid (TAK-242) i.v. administration at the beginning of thestress session completely blocks TLR-4 mRNA and protein upregulati

7、on after stress exposure 3.PROTOCOLCell Assay 1 RAW264.7 cells are seeded at a density of 3106 cells/well in six-well culture plate and incubated overnight.After washing with RPMI 1640 medium supplemented with 1% FCS and 10 g/mL Kanamycin, the cells arestimulated with 5 ng/mL LPS and 1 U/mL IFN- in

8、the presence or absence of Resatorvid (TAK-242) (1-100nM) for the indicated time. Culture supernatants are removed, and total RNA is isolated using the total RNAisolation reagent ISOGEN. Total RNA is reverse transcribed into cDNA by using TaqMan reversetranscription reagents. Quantitative real-time

9、PCR analysis of TNF- and IL-6 is performed on ABI Prism7700 using predeveloped TaqMan assay reagents and Universal PCR master mix. Quantitation of mRNA isperformed using the comparative threshold cycle method. The highest control level attained by thestimulation (without Resatorvid (TAK-242) is rega

10、rded as 100%, and the levels of control group at other timepoints and TAK-242-added group are expressed as the percentage of the highest control level 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 23 Thirty ApoE-/- and th

11、irty wild-type mice on C57BL/6 background (female, 10 weeks old) are fed on a high-fatdiet containing 0.25% cholesterol and 15% cocoa butter under standardized lighting conditions (12 h light-dark cycle) and temperature (211C). And mineral water is administered ad libitum. Mice of both genotypesare

12、randomly assigned to LPS or LPS + Resatorvid (TAK-242) or saline administration. LPS (2.5 mg/kg), LPS(2.5 mg/kg) plus Resatorvid (TAK-242) (0.3 mg/kg) and saline are administered respectively by2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEintraperitoneal injection, twice a week for 4 weeks. At t

13、he end of experiments, all mice underwent euthanasiawith injection of overdose pentobarbital (50 mg/kg).Rats 3Male outbred Wistar Hannover rats, initially weighing 200 to 225 g, are used. Resatorvid (TAK-242) is i.v.injected in the tail vein at a dose of 0.5 mg/kg immediately after (approximately 10

14、 seconds) introducing theanimal to the plastic restrainer. This dose is chosen on the basis of previous in vivo studies reporting its anti-inflammatory/antioxidant and neuroprotective profile in microglia exposed to hypoxia. Dimethyl sulphoxide ata concentration of 0.9% is used as vehicle.MCE has no

15、t independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Nat Commun. 2019 Mar 4;10(1):1015. Biomaterials. 2018 Mar;159:13-24. ACS Appl Mater Interfaces. 2019 Aug 7;11(31):27536-27547. Cancer Res. 2019 Mar 1;79(5):918-927. Cancer Res. 2016 Nov 15;76(22):6631-66

16、42.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Ii M, et al. A novel cyclohexene derivative, ethyl (6R)-6-N-(2-Chloro-4-fluorophenyl)sulfamoylcyclohex-1-ene-1-carboxylate (TAK-242),selectively inhibits toll-like receptor 4-mediated cytokine production through suppression of

17、intracellular signaling.2. Ni JQ, et al. Role of toll-like receptor 4 on lupus lung injury and atherosclerosis in LPS-challenge ApoE-/- mice. Clin Dev Immunol.2013;2013:476856.3. Grate I, et al. Toll-like 4 receptor inhibitor TAK-242 decreases neuroinflammation in rat brain frontal cortex after stre

18、ss. JNeuroinflammation. 2014 Jan 11;11:8.4. Wang L, et al. Doxorubicin-Induced Systemic Inflammation Is Driven by Upregulation of Toll-Like Receptor TLR4 and EndotoxinLeakage. Cancer Res. 2016 Nov 15;76(22):6631-6642.5. Shibata A, et al. Toll-like receptor 4 antagonist TAK-242 inhibits autoinflammatory symptoms in DITRA. J Autoimmun. 2017 Jun;80