TAK-242
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
IC50:在RAW264.7细胞和巨噬细胞中,TAK-242抑制LPS诱导的NO产生以及肿瘤坏死因子α和白细胞介素(IL)-6的产生,IC50为1.1-11 nM [1]。
Toll蛋白是Toll样受体(TLR)家族的成员,是果蝇胚胎背腹极性发育中至关重要的基因产物,对果蝇的抗真菌应答起关键作用。TAK-242(resatorvid)是环己烯衍生物,是选择性抑制TLR4信号的新型小分子化合物。
体外实验:体外研究表明,采用免疫共沉淀的方法,TAK-242通过结合TLR4胞内结构域,抑制脂多糖诱导的炎症介质的产生。10种不同的人TLRs中,TAK-242选择性地结合TLR4。这些结果表明,TAK-242可以选择性地结合TLR4,打乱TLR4与衔接分子的相互作用,从而抑制TLR4信号转导及其下游信号[2]。
在体实验:临床前动物研究表明急性应激上调大鼠 TLR-4的mRNA和蛋白水平的表达。 TAK-242阻止潜在的有害炎症和氧化/亚硝基介质在大鼠脑额叶皮层的积累。这些发现表明,TAK-242或其它TLR-4信号传导途径的抑制性化合物的使用可作为潜在的治疗辅助策略,用于治疗压力应激和压力相关的神经精神性疾病发生后的炎症过程[3]。
临床试验:为了评估Toll样受体4介导的信号传导的小分子抑制剂TAK-242是否能抑制细胞因子的水平,美国和欧洲武田药品有限公司(简称“武田”)在日本对严重脓毒症患者进行为期28天的全因死亡率研究。然而,研究结果表明, TAK-242不符合使用继续研发的标准,但这并不是受化合物安全性或有效性的影响[4]。
参考文献:
[1] Ii M, Matsunaga N, Hazeki K, Nakamura K, Takashima K, Seya T, Hazeki O, Kitazaki T, Iizawa Y. A novel cyclohexene derivative, ethyl (6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex- 1-ene-1-carboxylate (TAK-242), selectively inhibits toll-like receptor 4-mediated cytokine production through suppression of intracellular signaling. Mol Pharmacol. 2006;69(4):1288-95.?
[2] Naoko Matsunaga, Noboru Tsuchimori, Tatsumi Matsumoto, and Masayuki Ii. TAK-242 (Resatorvid), a Small-Molecule Inhibitor of Toll-Like Receptor (TLR) 4 Signaling, Binds Selectively to TLR4 and Interferes with Interactions between TLR4 and Its Adaptor Molecules. Mol Pharmacol 79:34–41, 2011
[3] Iciar Gárate, Borja García-Bueno, José Luis Mu?oz Madrigal, Javier R Caso, Luis Alou, María Luisa Gómez-Lus and Juan Carlos Leza. Toll-like 4 receptor inhibitor TAK-242 decreases neuroinflammation in rat brain frontal cortex after stress. Journal of Neuroinflammation 2014, 11:8
[4] Todd W. Rice; Arthur P. Wheeler; Gordon R. Bernard; Jean-Louis Vincent; Derek C. Angus; Naoki Aikawa; Ignace Demeyer; Stephen Sainati; Nicholas Amlot; Charlie Cao; Masayuki Ii; Hideyasu Matsuda; Kouji Mouri; Jon Cohen. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med 2010 Vol. 38, No. 8: 1-1
- 1. Xingjie Ping, Zhi Chai, et al. "Blocking receptor for advanced glycation end products (RAGE) or toll‐like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice." Epilepsia. 2021 Dec;62(12):3105-3116. PMID: 34535891
- 2. Liang Wang, Hui Shi, et al. "Astragaloside IV protects diabetic cardiomyopathy against inflammation and apoptosis via regulating TLR4/MyD88/NF-κB signaling pathway." Journal of Functional Foods 88 (2022) 104905.
- 3. Zhijing Zhang, Lideng Guo, et al. "Adiponectin attenuates splenectomy-induced cognitive deficits by alleviating neuroinflammation and oxidative stress via the TLR4/MyD88/NF-κb signaling pathway in aged rats." Research Square.
- 4. Haiyun Chen, Xiao Chang, et al. "Tetramethylpyrazine Derivative T-006 Ameliorates the Amyloid-β Plagues of Transgenic Alzhermer's Mice by Modulation of TLR4-mediated MyD88/NF-κB Signaling." Research Square. rs-1043837/v1.
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- 14. Guo LT, Wang SQ, et al. "Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway." J Neuroinflammation. 2019 May 8;16(1):95. PMID: 31068207
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Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 361.82 |
Cas No. | 243984-11-4 |
Formula | C15H17ClFNO4S |
Synonyms | Resatorvid;TAK242;TAK 242;CLI-095 |
Solubility | insoluble in H2O; ≥100.6 mg/mL in EtOH; ≥18.09 mg/mL in DMSO |
Chemical Name | ethyl (6R)-6-[(2-chloro-4-fluorophenyl)sulfamoyl]cyclohexene-1-carboxylate |
SDF | Download SDF |
Canonical SMILES | CCOC(=O)C1=CCCCC1S(=O)(=O)NC2=C(C=C(C=C2)F)Cl |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验 [1]: | |
LPS结合PBMC实验 |
将PBMC悬浮于BSA溶液(含0.1% BSA和0.01%叠氮化钠的磷酸盐缓冲盐水)中。在总体积为50 μL的体系中,将PBMC(3 × 105 个细胞)与TAK-242、抗人CD14单克隆抗体 (MAb) MEM-18,或抗人CC趋化因子受体5 (CCR5) MAb(作为阴性对照)一起置于4 ℃下孵育30分钟。在人血清存在的情况下,将细胞与50 ng/mL LPS(来源于结合了Alexa Fluor488的大肠杆菌血清型O55:B5,其终浓度为1%)置于37 ℃下进一步孵育45分钟。用BSA溶液洗涤2次后,通过CytoACE300细胞荧光计,采用流式细胞术分析1 × 104细胞。对于从4个不同供体所获得的PBMC样本,对每个样本均测定3次。LPS结合百分比为LPS结合细胞百分比之差(在LPS存在的情况下的值减去在LPS不存在的情况下的值)。 |
细胞实验 [2]: | |
细胞系 |
RAW264.7细胞 |
制备方法 |
可溶于DMSO。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
反应条件 |
1、10、100和1000 nM;15分钟 |
实验结果 |
在RAW264.7细胞中,TAK-242抑制LPS诱导的IRAK-1磷酸化。 |
动物实验 [3]: | |
动物模型 |
Wistar Hannover大鼠 |
给药剂量 |
0.5 mg/kg;静脉注射 |
实验结果 |
在大鼠脑额叶皮层中,TAK-242防止潜在的有害炎症和氧化/亚硝基介质积累。 |
其它注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: [1]. Ii M, Matsunaga N, Hazeki K, Nakamura K, Takashima K, Seya T, Hazeki O, Kitazaki T, Iizawa Y. A novel cyclohexene derivative, ethyl (6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex- 1-ene-1-carboxylate (TAK-242), selectively inhibits toll-like receptor 4-mediated cytokine production through suppression of intracellular signaling. Mol Pharmacol. 2006;69(4):1288-95. [2]. Naoko Matsunaga, Noboru Tsuchimori, Tatsumi Matsumoto, and Masayuki Ii. TAK-242 (Resatorvid), a Small-Molecule Inhibitor of Toll-Like Receptor (TLR) 4 Signaling, Binds Selectively to TLR4 and Interferes with Interactions between TLR4 and Its Adaptor Molecules. Mol Pharmacol 79:34–41, 2011. [3] Iciar Gárate, Borja García-Bueno, José Luis Mu?oz Madrigal, Javier R Caso, Luis Alou, María Luisa Gómez-Lus and Juan Carlos Leza. Toll-like 4 receptor inhibitor TAK-242 decreases neuroinflammation in rat brain frontal cortex after stress. Journal of Neuroinflammation 2014, 11:8. |
质量控制和MSDS
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