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: With IC50 of 1.1 to 11 nM, TAK-242 inhibited LPS-induced NO production, tumor necrosis factor-alpha and interleukin (IL)-6 in RAW264.7 cells and mouse peritoneal macrophages [1].
Toll, a member of the Toll-like receptor (TLR) family, was identified as a gene product essential for the development of embryonic dorsoventral polarity in Drosophila melanogaster. Moreover, it has been also found to play a critical role in the antifungal response of flies. TAK-242 (resatorvid), a cyclohexene derivative, is recongnizred as a novel small-molecule compound selectively inhibiting TLR4 signaling.
In vitro: A previous in-vitro study showed that TAK-242 could inhibit the production of lipopolysaccharide-induced inflammatory mediators by binding to the intracellular domain of TLR4 using coimmunoprecipitation approach. Among 10 different human TLRs, TAK-242 selectively bound to TLR4. These findings suggested that TAK-242 could selectively bind to TLR4 and disrupted the interaction of TLR4 with adaptor molecules, thereby inhibiting TLR4 signal transduction and its downstream signaling [2].
In vivo: Preclinical animal study demonostrated that the acute restraint stress exposure upregulateed TLR-4 expression both at the mRNA and protein level in rat. TAK-242 pre-stress administration prevented the accumulation of potentially deleterious inflammatory and oxidative/nitrosative mediators in the brain frontal cortex of rats. These finding s indicated that the use of TAK-242 or other TLR-4 signalling pathway inhibitory compounds could be considered as a potential therapeutic adjuvant strategy to constrain the inflammatory process taking place after stress exposure and in stress-related neuropsychiatric diseases [3].
Clinical trial: To evaluate whether TAK-242, a small-molecule inhibitor of Toll-like receptor-4–mediated signaling, suppresses cytokine levels and improves 28-day all-cause mortality rates in patients with severe sepsis has been conducted in Japan, the U.S. and Europe by Takeda Pharmaceutical Company Limited ("Takeda"). However, following a thorough review of development strategy, Takeda has concluded that TAK-242’s profile does not meet the criteria to support continuation of further development activities. This decision has not been influenced by any concerns over the safety or efficacy of the compound [4].
Reference:
[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: 1-10.
- 1. 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
- 2. Shao S, Fang H, et al. "Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk." Front Immunol. 2019 Apr 5;10:746. PMID:31024570
- 3. Dong X, Zheng Z, et al. "ACPAs promote IL-1βproduction in rheumatoid arthritis by activating the NLRP3 inflammasome." Cell Mol Immunol. 2019 Mar 25. PMID:30911117
- 4. Xue J, Ge H, et al. "The role of dendritic cells regulated by HMGB1/TLR4 signalling pathway in myocardial ischaemia reperfusion injury." J Cell Mol Med. 2019 Apr;23(4):2849-2862. PMID:30784177
- 5. Sun Y, Su J, et al. "Aflatoxin B(1) Promotes Influenza Replication and Increases Virus Related Lung Damage via Activation of TLR4 Signaling." Front Immunol. 2018 Oct 4;9:2297. PMID:30337931
- 6. Fanfan Xu, Xinghua Qiu, et al. "Effects on IL-1b signaling activation induced by water and organic extracts of fine particulate matter (PM2.5) in vitro*" Environmental Pollution 237 (2018) 592e600.
- 7. Zhu L, Han J, et al. "Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway." Biol Res. 2018 Mar 31;51(1):9. PMID:29604956
- 8. Gao X, Li T, et al. "Bacterial outer membrane vesicles from dextran sulfate sodium-induced colitis differentially regulate intestinal UDP-glucuronosyltransferase 1A1 partially through TLR4/MAPK/PI3K pathway." Drug Metab Dispos. 2018 Jan 8. pii:dmd.117.079046. PMID:29311138
- 9. Fellner A, Barhum Y, et al. "Toll-Like Receptor-4 Inhibitor TAK-242 Attenuates Motor Dysfunction and Spinal Cord Pathology in an Amyotrophic Lateral Sclerosis Mouse Model." Int J Mol Sci. 2017 Aug 1;18(8). pii: E1666. PMID:28763002
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 | ≥18.091 mg/mL in DMSO, ≥100.6 mg/mL in EtOH, <2.45 mg/mL in H2O |
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 |
Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request |
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. |
Kinase experiment [1]: | |
Assay for LPS binding to PBMCs |
PBMCs were suspended in BSA solution (phosphate-buffered saline containing 0.1% BSA and 0.01% sodium azide). In a total volume of 50 μL, PBMCs (3 × 105 cells) were incubated with TAK-242, anti-human CD14 monoclonal antibody (MAb) MEM-18, or anti-human CC-chemokine receptor 5 (CCR5) MAb as a negative control for 30 mins at 4 °C. The cells were further incubated with 50 ng/mL LPS from E. coli serotype O55:B5 conjugated with Alexa Fluor 488 per milliliter in the presence of human serum at a final concentration of 1% for 45 mins at 37 °C. After washing twice with BSA solution, 1 × 104 cells were analyzed by flow cytometry using CytoACE300 cytofluorometer. The assays were performed in triplicate for each preparation of PBMCs obtained from four different donors. Specific LPS binding was estimated by subtracting the percentage of LPS-binding cells in the absence of LPS from that in the presence of LPS. |
Cell experiment [2]: | |
Cell lines |
RAW264.7 cells |
Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions |
1, 10, 100 and 1000 nM; 15 mins |
Applications |
In RAW264.7 cells, TAK-242 inhibited the phosphorylation of IRAK-1 induced by LPS. |
Animal experiment [3]: | |
Animal models |
Wistar Hannover rats |
Dosage form |
0.5 mg/kg; i.v. |
Applications |
TAK-242 prevented the accumulation of potentially deleterious inflammatory and oxidative/nitrosative mediators in the brain frontal cortex of rats. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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. |
Quality Control & MSDS
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Chemical structure

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