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Resatorvid (TAK-242) TLR4 inhibitor

Name: Resatorvid (TAK-242)
Brand: Selleck Chemicals
SKU: S7455
Rating: 5 (63 reviews)

Cat.No.S7455

Resatorvid (TAK-242, CLI-095) is a small-molecule-specific inhibitor of Toll-like receptor (TLR) 4 signaling, blocking LPS-induced production of NO, TNF-alpha and IL-6 in macrophages with IC50 of 1.8 nM, 1.9 nM and 1.3 nM, respectively. This compound downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF, and it also inhibits Autophagy.

Chemical Structure

Molecular Weight: 361.82

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Quality Control

Batch: Purity: 99.92%

99.92

Related Targets	PD-1/PD-L1 CXCR STING AhR Immunology & Inflammation related CD markers Interleukins Anti-infection Antioxidant COX
Other TLR Inhibitors	Resiquimod (R-848) FSL-1 TLR2-IN-C29 Lipopolysaccharides (LPS) Motolimod CU-CPT22 TLR4-IN-C34 Vesatolimod (GS-9620) E6446 E6446 Dihydrochloride

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
RAW264.7	Function assay		Inhibition of LPS-induced IL6 production in mouse RAW264.7 cells by ELISA, IC50 = 0.0013 μM.	16279805
RAW264.7	Function assay		Inhibition of LPS-induced nitric oxide production in mouse RAW264.7 cells, IC50 = 0.0018 μM.	16279805
RAW264.7	Function assay		Inhibition of LPS-induced TNFalpha production in mouse RAW264.7 cells by ELISA, IC50 = 0.0019 μM.	16279805
HEK-Blue	Function assay	2 hrs	Inhibition of human TLR4 signaling expressed in HEK-Blue cells co-expressing MD2/CD14 assessed as reduction in LPS-induced NF-kappaB activation-mediated SEAP production preincubated for 2 hrs followed by LPS stimulation for 20 hrs by colorimetric assay, IC50 = 0.68 μM.	29472126
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	361.82	Formula	C₁₅H₁₇ClFNO₄S	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	243984-11-4	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	CLI-095			Smiles	CCOC(=O)C1=CCCCC1S(=O)(=O)NC2=C(C=C(C=C2)F)Cl

Solubility

In vitro
Batch:

DMSO : 72 mg/mL (198.99 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 72 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	1%DMSO 1 40%PEG300 2 5%TWEEN80 3 54%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.600mg/ml (1.66mM)	Taking the 1 mL working solution as an example, add 10 μL of 60 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 540 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.100mg/ml (14.10mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 102 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	2%DMSO 1 98%Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.400mg/ml (1.11mM)	Taking the 1 mL working solution as an example, add 20 μL of 20 mg/ml clear DMSO stock solution to 980 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	TLR4 IL-6 (Cell-free assay) 1.3 nM NO (Cell-free assay) 1.8 nM TNF-α (Cell-free assay) 1.9 nM
In vitro	Resatorvid (TAK-242) inhibits the TLR4 pathway by binding directly to a Cys747 in the intracellular TLR4 domain. It disrupts the interactions of TLR4 with its adaptor molecules, TIRAP and TRAM.
In vivo	Resatorvid (TAK-242) protects against acute cerebral ischemia/reperfusion injury in mice by dose of 3 mg/kg. Topical application of this compound can block UV-induced AP-1 activation in mouse epidermis. In a UV-induced skin tumorigenesis model, it displays potent photochemopreventive activity, significantly suppressing tumour area and multiplicity. Tumours harvested from resatorvid-treated mice display reduced activity of UV-associated signalling pathways and a corresponding increase in apoptosis compared to tumours from control animals. It also significantly reduces the neuronal damage occurring after cerebral ischemia, a form of stroke in mice.
References	[1] https://pubmed.ncbi.nlm.nih.gov/28976923/ [2] https://pubmed.ncbi.nlm.nih.gov/29437671/ [3] https://pubmed.ncbi.nlm.nih.gov/23193438/ [4] https://www.ncbi.nlm.nih.gov/pubmed/?term=27859308 [5] https://pubmed.ncbi.nlm.nih.gov/16279805/

Applications

Methods	Biomarkers	Images	PMID
Western blot	TLR4 / p-p65 / p65 / pIκBα / IκBα Bcl-2 / Cleaved caspase-3		29207635
Immunofluorescence	TLR4 NFκB		29311802

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04620148	Unknown status	Acute-On-Chronic Liver Failure	Akaza Bioscience Ltd\|Iqvia Pty Ltd	December 2021	Phase 2

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