Resatorvid (TAK-242) 是一种选择性的TLR4信号传导抑制剂。Resatorvid 抑制NO，TNF-α和IL-6的产生，其IC50值分别为 1.8 nM，1.9 nM，1.3 nM。Resatorvid 下调TLR4下游信号分子 MyD88 和 TRIF 的表达。Resatorvid 抑制自噬 (autophagy)，并在各种炎症性疾病中起关键作用。
| 生物活性 | Resatorvid (TAK-242) is a selectiveToll-like receptor 4 (TLR4)inhibitor. Resatorvid inhibitsNO, TNF-αandIL-6production withIC50sof 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression ofTLR4downstream signaling moleculesMyD88and TRIF. Resatorvid inhibitsautophagyand plays pivotal role in various inflammatory diseases[1][2]. |
| IC50& Target[1][2] | TLR4 | IL-6 1.3 nM (IC50) | TNF-R 1.9 nM (IC50) |
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体外研究
(In Vitro) | Resatorvid suppresses the production of NO, TNF-α, and IL-6 from LPS-stimulated human peripheral blood mononuclear cells (PBMCs) atIC50values from 11 to 33 nM[1].
Resatorvid (1-100 nM; 4 hours) inhibits mRNA expression of IL-6 and TNF-α induced by LPS and IFN-γ in RAW264.7 cells[1].
Resatorvid (1-100 nM; 15 minutes; PBMCs cells) markedly inhibits the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), p38, and JNK/SAPK as well as degradation of IκBβ at a concentration of 100 nM[1].
RT-PCR[1] | Cell Line: | RAW264.7 cells | | Concentration: | 1 nM, 10 nM, 100 nM | | Incubation Time: | 4 hours | | Result: | TNF-α and IL-6 mRNA expression levels were clearly suppressed at concentrations of 10 to 100 nM. |
Western Blot Analysis[1] | Cell Line: | PBMCs cells | | Concentration: | 1 nM, 10 nM, 100 nM | | Incubation Time: | 15 minutes | | Result: | The phosphorylation of mitogen-activated protein kinases induced by LPS was also inhibited in a concentration-dependent manner. |
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体内研究
(In Vivo) | Resatorvid (TAK-242; 3 mg/kg; intraperitoneal injection; for 2 days; male C57BL/6 mice) pretreatment markedly and significantly reverses the LPS-induced body weight loss, TA muscle loss, and muscle strength loss. TAK-242 reverses the LPS-induced shrinkage of muscle fibres and increases the interstitial space. TAK-242 blocks systemic catabolic cytokine release and skeletal muscle proteolysis in LPS-administered mice[3].
| Animal Model: | Male C57BL/6 mice (8-12 weeks of age) treated with lipopolysaccharide (LPS)[3] | | Dosage: | 3 mg/kg | | Administration: | Intraperitoneal injection; for 2 days | | Result: | Pretreatment of mice reduced or reversed all the detrimental effects of LPS. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(276.38 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.7638 mL | 13.8190 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 |
*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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方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，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: 5.5 mg/mL (15.20 mM); Suspended solution; Need ultrasonic 2. 请依序添加每种溶剂： 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: 5.5 mg/mL (15.20 mM); Suspended solution; Need ultrasonic 3. 请依序添加每种溶剂： 10% DMSO 90% saline Solubility: 5 mg/mL (13.82 mM); Suspended solution; Need ultrasonic 4. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.75 mg/mL (7.60 mM); Clear solution
此方案可获得 ≥ 2.75 mg/mL (7.60 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 5. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.75 mg/mL (7.60 mM); Suspended solution; Need ultrasonic
此方案可获得 2.75 mg/mL (7.60 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 6. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.75 mg/mL (7.60 mM); Clear solution
此方案可获得 ≥ 2.75 mg/mL (7.60 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 7. 请依序添加每种溶剂： 5% DMSO 95% saline Solubility: 2.5 mg/mL (6.91 mM); Suspended solution; Need ultrasonic 8. 请依序添加每种溶剂： 1% DMSO 99% saline Solubility: 0.5 mg/mL (1.38 mM); Suspended solution; Need ultrasonic *以上所有助溶剂都可在本网站选购。
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