TAK-242 (Resatorvid)

Biological Activity

Resatorvid (TAK-242) is a selective TLR4 signaling inhibitor. Resatorvid inhibited the production of NO, TNF-α and IL-6 with IC50 values of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid down-regulates the expression of MyD88 and TRIF signaling molecules downstream of TLR4. Resatorvid inhibits autophagy and plays a key role in a variety of inflammatory diseases.

Product Citations

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  Chem Biodivers. 2023 Jan 18.

  Cinnamaldehyde ameliorates dextran sulfate sodium‐induced colitis in mice by modulating TLR4/NF‐κB signaling pathway and NLRP3 inflammasome activation
  TAK-242 (Resatorvid) purchased from AbMole

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  Thromb Res. 2023 Feb;222:49-62.

  High mobility group box 1 derived mainly from platelet microparticles exacerbates microvascular obstruction in no reflow
  TAK-242 (Resatorvid) purchased from AbMole

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  Front Immunol. 2022 Jul 8;13:901566.

  Hepatocyte-Conditional Knockout of Phosphatidylethanolamine Binding Protein 4 Aggravated LPS/D-GalN-Induced Acute Liver Injury via the TLR4/NF-κB Pathway
  TAK-242 (Resatorvid) purchased from AbMole

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  Animals (Basel). 2021 Dec 1;11(12):3422..

  NF-κB–Dependent Snail Expression Promotes Epithelial–Mesenchymal Transition in Mastitis
  TAK-242 (Resatorvid) purchased from AbMole

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  Clinics (Sao Paulo). 2021 Mar 8;76:e2484.

  miR-139-5p protects septic mice with acute lung injury by inhibiting Toll-like receptor 4/Myeloid differentiation factor 88/Nuclear factor-&mac_kgr;B signaling pathway
  TAK-242 (Resatorvid) purchased from AbMole

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  Mar Drυgs. 2020 Oct 28;18(11):538.

  Immunostimulatory Effects of Polysaccharides from Spirulina platensis In Vivo and Vitro and Their Activation Mechanism on RAW246.7 Macrophages
  TAK-242 (Resatorvid) purchased from AbMole

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  Mar Drυgs. 2020 Aug 17;18(8):429.

  Comparison of Physicochemical Characteristics and Macrophage Immunostimulatory Activities of Polysaccharides from Chlamys farreri
  TAK-242 (Resatorvid) purchased from AbMole

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  Biochem Biophys Res Commun. 2020 Oct 22;531(4):602-608.

  Toll-like receptor 4 plays a key role in advanced glycation end products-induced M1 macrophage polarization
  TAK-242 (Resatorvid) purchased from AbMole

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  J Clin Invest. 2020 May 19.

  Residual endotoxin induces primary graft dysfunction through ischemia-reperfusion-primed alveolar macrophages
  TAK-242 (Resatorvid) purchased from AbMole

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  Cell Mol Neurobiol. 2019 Mar;39(2):301-319.

  Myosin IIA Regulated Tight Junction in Oxygen Glucose-Deprived Brain Endothelial Cells Via Activation of TLR4/PI3K/Akt/JNK1/2/14-3-3ε/NF-κB/MMP9 Signal Transduction Pathway.
  TAK-242 (Resatorvid) purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Mar Drugs (2020), Figure 9, TAK-242 (Abmole Bioscience)
	Method	pre-incubated cells
	Cell Lines	RAW264.7 cells
	Concentrations	10 µmol/L
	Incubation Time	1h
	Results	This result suggested that TLR4 was one of the receptors of PSP-L on RAW264.7 cells and may be the vital one.

	Source	Mar Drugs (2020), Figure 8, TAK-242 (Abmole Bioscience)
	Method	pre-incubated cells
	Cell Lines	RAW264.7 cells
	Concentrations	10 µmol/L
	Incubation Time	1h
	Results	This result suggested that TLR4 was one of the receptors of PSP-L on RAW264.7 cells and may be the vital one.

	Source	Oncotarget (2018). Figure 3. TAK-242
	Method	Western blotting
	Cell Lines	RA-FLS cells
	Concentrations	-
	Incubation Time	24, 48 and 72 h.
	Results	As shown in Figure 3, the protein and mRNA expressions of TLR4 and NF-κB decreased in the miR-146a mimic and the Tak-242 groups, while mRNA and protein expressions of TLR4 and NF- κB increased in the miR-146a inhibitor and the TLR4 groups, and the mRNA and protein expressions of TLR4 and NF-κB in the TLR4 group were significantly higher than those in the miR-146a inhibitor group

Protocol (for reference only)

Cell Experiment
Cell lines	L6-GLUT4myc
Preparation method	Prior to treatment with LPS or stearate, cells were pre-treated with TAK-242 (1 μM) or vehicle control for 1 h. TAK-242 remained in culture medium for the duration for the experiment.
Concentrations	1 μM
Incubation time	1 h

Animal Experiment
Animal models	C57Bl/6 mice
Formulation	5% DMSO, 5% Tween80
Dosages	3 mg/kg
Administration	i.v.

Chemical Information

Molecular Weight	361.82
Formula	C15H17ClFNO4S
CAS Number	243984-11-4
Solubility (25°C)	DMSO 80 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Fei Xing, et al. Mol Pain. TLR4/NF-κB signaling activation in plantar tissue and dorsal root ganglion involves in the development of postoperative pain

[2] Woller SA, et al. Brain Behav Immun. Systemic TAK-242 prevents intrathecal LPS evoked hyperalgesia in male, but not female mice and prevents delayed allodynia following intraplantar formalin in both male and female mice: The role of TLR4 in the evolution of a persistent pain state

[3] Hussey SE, et al. Biosci Rep. TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipid-induced inflammation and insulin resistance in muscle cells.

[4] Takuryu Sha, et al. Shock. Combination of imipenem and TAK-242, a Toll-like receptor 4 signal transduction inhibitor, improves survival in a murine model of polymicrobial sepsis