TAK-242 (Resatorvid) 瑞沙托维

生物活性

TAK-242 (Resatorvid) is a small-molecule-specific inhibitor of Toll-like receptor (TLR) 4 signaling. TAK-242 inhibits the production of lipopolysaccharide-induced inflammatory mediators by binding to the intracellular domain of TLR4. TAK-242 also inhibited mRNA expression of IL-6 and TNF-alpha induced by LPS and interferon-gamma in RAW264.7 cells. TAK-242 suppressed the production of these cytokines from LPS-stimulated human peripheral blood mononuclear cells (PBMCs) at IC50 values from 11 to 33 nM. Intravenous administration of TAK-242 to mice 1 h before LPS challenge dose-dependently inhibited LPS-induced increases in serum levels of TNF-alpha, IL-1beta, IL-6, IL-10, MIP-2, and NO metabolites. TAK-242 protected mice from LPS-induced lethality in a similar dose-dependent manner, and rescued 100% of mice at a dose of 1 mg/kg.

使用AbMole产品发表的文献

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  Cinnamaldehyde ameliorates dextran sulfate sodium‐induced colitis in mice by modulating TLR4/NF‐κB signaling pathway and NLRP3 inflammasome activation

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  Myosin IIA Regulated Tight Junction in Oxygen Glucose-Deprived Brain Endothelial Cells Via Activation of TLR4/PI3K/Akt/JNK1/2/14-3-3ε/NF-κB/MMP9 Signal Transduction Pathway.

产品使用成果展示

	数据来源	Mar Drugs (2020), Figure 9, TAK-242 (Abmole Bioscience)
	方法	pre-incubated cells
	细胞系/动物模型	RAW264.7 cells
	浓度	10 µmol/L
	处理时间	1h
	实验结果	This result suggested that TLR4 was one of the receptors of PSP-L on RAW264.7 cells and may be the vital one.

	数据来源	Mar Drugs (2020), Figure 8, TAK-242 (Abmole Bioscience)
	方法	pre-incubated cells
	细胞系/动物模型	RAW264.7 cells
	浓度	10 µmol/L
	处理时间	1h
	实验结果	This result suggested that TLR4 was one of the receptors of PSP-L on RAW264.7 cells and may be the vital one.

	数据来源	Oncotarget (2018). Figure 3. TAK-242
	方法	Western blotting
	细胞系/动物模型	RA-FLS cells
	浓度	-
	处理时间	24, 48 and 72 h.
	实验结果	As shown in Figure 3, the protein and mRNA expressions of TLR4 and NF-κB decreased in the miR-146a mimic and the Tak-242 groups, while mRNA and protein expressions of TLR4 and NF- κB increased in the miR-146a inhibitor and the TLR4 groups, and the mRNA and protein expressions of TLR4 and NF-κB in the TLR4 group were significantly higher than those in the miR-146a inhibitor group

实验参考

体外实验*
细胞系	L6-GLUT4myc
方法	Prior to treatment with LPS or stearate, cells were pre-treated with TAK-242 (1 μM) or vehicle control for 1 h. TAK-242 remained in culture medium for the duration for the experiment.
浓度	1 μM
处理时间	1 h

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	C57Bl/6 mice
配制	5% DMSO, 5% Tween80
剂量	3 mg/kg
给药处理	i.v.

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	361.82
分子式	C15H17ClFNO4S
CAS号	243984-11-4
溶解性（25°C）	DMSO 80 mg/mL
储存条件	粉末型式       -20°C   3年；4°C   2年 溶于溶剂       -80°C   6个月；-20°C   1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.7638 mL	13.819 mL	27.6381 mL
5 mM	0.5528 mL	2.7638 mL	5.5276 mL
10 mM	0.2764 mL	1.3819 mL	2.7638 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Fei Xing, et al. Mol Pain. TLR4/NF-κB signaling activation in plantar tissue and dorsal root ganglion involves in the development of postoperative pain

[2] Woller SA, et al. Brain Behav Immun. Systemic TAK-242 prevents intrathecal LPS evoked hyperalgesia in male, but not female mice and prevents delayed allodynia following intraplantar formalin in both male and female mice: The role of TLR4 in the evolution of a persistent pain state

[3] Hussey SE, et al. Biosci Rep. TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipid-induced inflammation and insulin resistance in muscle cells.

[4] Takuryu Sha, et al. Shock. Combination of imipenem and TAK-242, a Toll-like receptor 4 signal transduction inhibitor, improves survival in a murine model of polymicrobial sepsis