瑞沙托维作用机制 - Medchemexpress - MCE中国

1、Product Data SheetResatorvidCat. No.: HY-11109CAS No.: 243984-11-4分式: CHClFNOS分量: 361.82作靶点: Toll-like Receptor (TLR); TNF Receptor; Interleukin Related; Autophagy作通路: Immunology/Inflammation; Apoptosis; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO :

2、100 mg/mL (276.38 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.7638 mL 13.8190 mL 27.6381 mL5 mM 0.5528 mL 2.7638 mL 5.5276 mL10 mM 0.2764 mL 1.3819 mL 2.7638 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C,

3、 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.75 mg/mL

4、(7.60 mM); Clear solution此案可获得 2.75 mg/mL (7.60 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 27.5 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 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 ultrasonicPage

5、1 of 2 www.MedChemE此案可获得 2.75 mg/mL (7.60 mM) 的均匀悬浊液，悬浊液可于服和腹腔注射。以 1 mL 作液为例，取 100 L 27.5 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.75 mg/mL (7.60 mM); Clear solution此案可获得 2.75 mg/mL (7.60 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L

6、 27.5 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Resatorvid (TAK-242)种选择性的 TLR4 信号传导抑制剂。Resatorvid 抑制 NO，TNF-R 和 IL-6 的产，其 IC50 值分别为 1.8 nM，1.9 nM，1.3 nM。Resatorvid 下调 TLR4 下游信号分 MyD88 和 TRIF 的表达。Resatorvid 抑制噬 (autophagy)，并在各种炎症性疾病中起关键作。IC & Target TLR4 TNF-R IL-61.9 nM (IC50) 1.3 nM

7、(IC50)体外研究 Resatorvid suppresses the production of NO, TNF-, and IL-6 from LPS-stimulated human peripheral bloodmononuclear cells (PBMCs) at IC50 values from 11 to 33 nM1.Resatorvid (1-100 nM; 4 hours) inhibits mRNA expression of IL-6 and TNF- induced by LPS and IFN- in RAW264.7cells1.Resatorvid (1-

8、100 nM; 15 minutes; PBMCs cells) markedly inhibits the LPS-induced phosphorylation of extracellularsignal-regulated kinase 1/2 (Erk1/2), p38, and JNK/SAPK as well as degradation of IB at a concentration of 100 nM1.RT-PCR1Cell Line: RAW264.7 cellsConcentration: 1 nM, 10 nM, 100 nMIncubation Time: 4 h

9、oursResult: TNF- and IL-6 mRNA expression levels were clearly suppressed at concentrations of10 to 100 nM.Western Blot Analysis1Cell Line: PBMCs cellsConcentration: 1 nM, 10 nM, 100 nMIncubation Time: 15 minutesResult: The phosphorylation of mitogen-activated protein kinases induced by LPS was alsoi

10、nhibited in a concentration-dependent manner.体内研究Resatorvid (TAK-242; 3 mg/kg; intraperitoneal injection; for 2 days; male C57BL/6 mice) pretreatment markedly andsignificantly reverses the LPS-induced body weight loss, TA muscle loss, and muscle strength loss. TAK-242 reversesthe LPS-induced shrinka

11、ge of muscle fibres and increases the interstitial space. TAK-242 blocks systemic cataboliccytokine release and skeletal muscle proteolysis in LPS-administered mice3.Page 2 of 3 www.MedChemEAnimal Model: Male C57BL/6 mice (8-12 weeks of age) treated with lipopolysaccharide (LPS)3Dosage: 3 mg/kgAdmin

12、istration: Intraperitoneal injection; for 2 daysResult: Pretreatment of mice reduced or reversed all the detrimental effects of LPS.户使本产品发表的科研献 Nat Commun. 2019 Mar 4;10(1):1015. Biomaterials. 2020 May;241:119852. Biomaterials. 2018 Mar;159:13-24. ACS Appl Mater Interfaces. 2019 Aug 7;11(31):27536-2

13、7547. Cancer Res. 2019 Mar 1;79(5):918-927.See more customer validations on HYPERLINK www.MedChemE 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), selectivelyinhibits toll-like receptor 4-m

14、ediated cytokine production through suppression of intracellular signaling.2. Yamada M, et al. Discovery of novel and potent small-molecule inhibitors of NO and cytokine production as antisepsis agents: synthesis and biologicalactivity of alkyl 6-(N-substituted sulfamoyl)cyclohex-1-ene-1-carboxylate. J Med Chem. 2005 Nov 17;48(23):7457-67.3. Yuko Ono, et al. TAK-242, a Specific Inhibitor of Toll-like Receptor 4 Signalling, Prevents Endotoxemia-Induced Skeletal Muscle Wasting in Mice. Sci Rep.2020 Jan 20;10(1):694.M