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Purity: = 99.67%
Resatorvid (formerly also known as TAK-242) is a novel, cell-permeable and potent TLR4 (Toll-Like Receptor) signaling inhibitor with immunomodulatory and anti-inflammatory activity. It selectively inhibits the TLR4-mediated production of cytokines and nitric oxide. Resatorvid blocks LPS-induced production of NO, TNF-α, IL-6, and IL-1β in macrophages with IC50 values of 1-11 nM. Resatorvid binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules. Resatorvid provides neuroprotection in experimental traumatic brain injury: implication in the treatment of human brain injury.
| Targets |
TLR4; TNF-R (IC50 = 1.9 nM); IL-6 (IC50 = 1.3 nM)
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|---|---|
| ln Vitro |
Resatorvid has IC50 values ranging from 11 to 33 nM, which suppresses NO, TNF-α, and IL-6 produced by LPS-stimulated human peripheral blood mononuclear cells (PBMC) [1]. At a dose of 100 nM, Resatorvid (1-100 nM; 4 hours) phosphorylates and destroys IκBβ. Resatorvid (1-100 nM; 15 minutes; PBMCs cells) strongly suppresses LPS-induced extracellular signal regulation model 1/2 (Erk1/2), p38, and JNK /SAPK [1].
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| ln Vivo |
LPS-induced weight loss, TA muscle loss, and muscular strength loss were all dramatically and significantly restored by resporvid (TAK-242; 3 mg/kg; i.p.; for 2 days; male C57BL/6 mice). TAK-242 increases interstitial space and reverses the contraction of muscle fibers produced by LPS. In mice given LPS, TAK-242 inhibits the release of catabolic cytokines into the system and the proteolysis of skeletal muscle [3].
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| Enzyme Assay |
The phosphorylation of mitogen-activated protein kinases induced by LPS was also inhibited in a concentration-dependent manner. However, TAK-242 did not antagonize the binding of LPS to the cells. It is noteworthy that TAK-242 suppressed the cytokine production induced by Toll-like receptor (TLR) 4 ligands, but not by ligands for TLR2, -3, and -9. In addition, IL-1β-induced IL-8 production from human PBMCs was not markedly affected by TAK-242. These data suggest that TAK-242 suppresses the production of multiple cytokines by selectively inhibiting TLR4 intracellular signaling. Finally, TAK-242 is a novel small molecule TLR4 signaling inhibitor and could be a promising therapeutic agent for inflammatory diseases, whose pathogenesis involves TLR4 [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: PBMC Cell Tested Concentrations: 1 nM, 10 nM, 100 nM Incubation Duration: 15 min Experimental Results: LPS-induced phosphorylation of mitogen-activated protein kinase was also inhibited in a concentration-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (8-12 weeks of age) treated with lipopolysaccharide (LPS)[3]
Doses: 3 mg/kg Route of Administration: intraperitoneal (ip)injection; for 2 days Experimental Results: Pretreatment of mice decreased or reversed all the detrimental effects of LPS. |
| References |
[1]. Ii M, et al. 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.2006 Apr;69(4):1288-95.
[2]. Yamada M, et al. Discovery of novel and potent small-molecule inhibitors of NO and cytokine production as antisepsis agents: synthesis and biological activity of alkyl 6-(N-substituted sulfamoyl)cyclohex-1-ene-1-carboxylate. J Med Chem. 2005 Nov 17;48(23):7457-67. [3]. Yuko Ono, 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. |
| Molecular Formula |
C15H17CLFNO4S
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|---|---|
| Molecular Weight |
361.82
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| Exact Mass |
361.05508
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| Elemental Analysis |
C, 49.80; H, 4.74; Cl, 9.80; F, 5.25; N, 3.87; O, 17.69; S, 8.86
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| CAS # |
243984-11-4
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| Appearance |
Off-white to yellow solid
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| LogP |
3.58
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| tPSA |
80.85
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| SMILES |
FC1=CC(Cl)=C(NS([C@@H]2CCCC=C2C(OCC)=O)(=O)=O)C=C1
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| InChi Key |
LEEIJTHMHDMWLJ-CQSZACIVSA-N
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| InChi Code |
InChI=1S/C15H17ClFNO4S/c1-2-22-15(19)11-5-3-4-6-14(11)23(20,21)18-13-8-7-10(17)9-12(13)16/h5,7-9,14,18H,2-4,6H2,1H3/t14-/m1/s1
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| Chemical Name |
ethyl (R)-6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate
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| Synonyms |
TAK242; TAK 242; TAK-242
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~276.38 mM)
Ethanol : ~20 mg/mL (~55.28 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5.5 mg/mL (15.20 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 5.5 mg/mL (15.20 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 5 mg/mL (13.82 mM) in 10% DMSO + 90% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: ≥ 2.75 mg/mL (7.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: 2.75 mg/mL (7.60 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 6: ≥ 2.75 mg/mL (7.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 7: 2.5 mg/mL (6.91 mM) in 5% DMSO + 95% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 8: 0.5 mg/mL (1.38 mM) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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