TAK-242 (Synonyms: Resatorvid) |
Catalog No.GC16148 |
A TLR4 antagonist
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 243984-11-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment [1]: | |
Cell lines |
HEK293, HEK293-hTLR4/MD2-CD14 |
Preparation Method |
HEK293 cells were cultured in DMEM supplemented with 10% heat-inactivated FCS, and 50 μg/ml gentamicin. HEK293-hTLR4 /MD2-CD14 cells were cultured in DMEM supplemented with 10% FCS, 10 μg/ml blasticidin, 50 μg/ml HygroGold, and 100 μg/ml Normocin. Cells were plated in a 96-well plate at a density of ~5 x 105 cells/well in RPMI 1640 supplemented with 10% FCS and incubated for 2 h at 37°C in a humidified incubator containing 5% CO2. Then the cells were washed with RPMI 1640 containing 10% FCS to eliminate nonadherent cells. TAK-242 was dissolved in N,N-dimethylformamide. |
Reaction Conditions |
HEK293 cells were transfected with expression vectors encoding FLAG-TLR4, MD-2, and FLAG-TIRAP or expression vectors encoding FLAG-TLR4, MD-2, and FLAG-TRAM. Six hours after transfection, the cells were incubated with various concentrations of TAK-242 (10, 100, 1000 nM) at 37°C. |
Applications |
TAK-242 inhibited the association of TIRAP with TLR4 and the association of TRAM with TLR4. TAK-242 also modulated the formation of the signaling complex containing the proximal elements in TLR4 signaling. TAK-242 also interferes with the interaction of TRAM and TLR4, inhibiting both NF-γB and ISRE activation and cytokine/interferon gene expression. |
Animal experiment [2]: | |
Animal models |
Male C57BL/6 mice, 6–8 weeks old, weighing 22–25 g |
Preparation Method |
C57BL/6 mice were randomly assigned to the LPS/D-GalN administration group and the TAK-242 + LPS/DGalN treatment group. Mice in the pretreatment group were injected with TAK-242 intraperitoneally 3h before mice were injected intraperitoneally with LPS (10 μg/kg)/D-GalN. |
Dosage form |
5 mg/kg |
Applications |
TAK-242 pretreatment improved LPS/D-GalN-induced FH in mice. Moreover, TAK-242 has anti-inflammatory effects in mice with concanavalin A-induced acute hepatitis. TAK-242 protected the liver by regulating MDSCs and the inhibition of TLR4 provided by TAK-242 significantly reduced the inflammatory response in FH. |
References: [1]. Matsunaga N, et al. 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. 2011 Jan;79(1):34-41. [2]. Wang H, et al. Toll-like Receptor 4 Inhibitor TAK-242 Improves Fulminant Hepatitis by Regulating Accumulation of Myeloid-Derived Suppressor Cell. Inflammation. 2021 Apr;44(2):671-681. |
TAK 242 is a toll-like receptor 4 (TLR4) signaling inhibitor. Binds to intracellular domain of TLR4. Inhibits LPS-induced cytokine production in vitro (IC50 values are 1.3, 1.3 and 3.2 nM for IL-6, TNFα and NO production).?TAK-242 binds to the TIR domain of TLR4 via Cys747,[1] and inhibits MyD88 and TRIF-dependent pathway. Previous studies showed that TAK-242 prevented acute kidney injury and lung injury in LPS-injected sheep and mice. What’s more, TAK-242 has also been tested in a clinical trial of patients with sepsis and was found to be well tolerated. It is also researched to have the usage as a therapeutic strategy for endotoxemia-associated muscle weakness.[2]
In vitro study demonstrated that TAK-242 disrupts the interactions of TLR4 with its adaptor molecules, TIRAP and TRAM. TAK-242 inhibited the association of TIRAP with TLR4 and the association of TRAM with TLR4. The inhibitory effect of TAK-242 may result from the direct action of TAK-242 on TLR4 without requiring the induction of intermediate gene expression or de novo protein synthesis. Moreover, strong evidence was provided that TAK-242 modulates the formation of the signaling complex containing the proximal elements in TLR4 signaling. TAK-242 inhibited TIRAP mediated NF-γB activation and TRAM-mediated NF-γB and ISRE activation in the presence of TLR4/MD-2. In addition, TAK-242 also inhibited LPS-induced NF-γB and ISRE activations in HEK293-hTLR4/MD2-CD14 cells. These results indicated that TAK-242 impairs the ability of TLR4 to associate with adaptor molecules and blocks subsequent signal transduction.[1]
In vivo experiments indicated that TAK-242 effectively reduced the severity of acute liver failure and increased the survival rate of FH mice. Mechanistically, the hepatoprotective effect of TAK-242 was related to inhibiting inflammation, reducing oxidative stress, and increasing the proportion of MDSCs. Results suggested that TAK-242 is a potent TLR4 inhibitor and would be a potential drug to protect against acute liver failure.[3]
References:
[1]. Matsunaga N, et al. 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. 2011 Jan;79(1):34-41.
[2]. Ono Y, 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.
[3]. Wang H, et al. Toll-like Receptor 4 Inhibitor TAK-242 Improves Fulminant Hepatitis by Regulating Accumulation of Myeloid-Derived Suppressor Cell. Inflammation. 2021 Apr;44(2):671-681.
Cas No. | 243984-11-4 | SDF | |
Synonyms | Resatorvid | ||
Chemical Name | ethyl (6R)-6-[(2-chloro-4-fluorophenyl)sulfamoyl]cyclohexene-1-carboxylate | ||
Canonical SMILES | CCOC(=O)C1=CCCCC1S(=O)(=O)NC2=C(C=C(C=C2)F)Cl | ||
Formula | C15H17ClFNO4S | M.Wt | 361.82 |
Solubility | ≥ 18.091 mg/mL in DMSO, ≥ 100.6 mg/mL in EtOH | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
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 |
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