| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
TLR4 (toll-like receptor 4). M62812 is a TLR4 signaling inhibitor that blocks LPS-induced TLR4 activation. By inhibiting TLR4 signaling, it suppresses the activation of endothelial cells and leukocytes, reduces pro-inflammatory cytokine production, and prevents the procoagulant effects associated with sepsis. TLR4 is a key receptor for bacterial lipopolysaccharide (LPS) and plays a central role in innate immune responses.
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| ln Vitro |
With an IC50 of 2.4 μg/mL, M62812 (10 μg/mL; 6 h) totally blocks LPS-induced NF-κB activation in NF-κB luciferase-expressing cells[1]. With an IC50 of 0.7 μg/mL, M62812 (3 μg/mL; 6 h) totally suppresses TNF-α production in peripheral blood mononuclear cells stimulated by LPS[1]. In human endothelial cells, M62812 (3 μg/mL; 6 h) totally suppresses the production of IL-6 and E-selection, with IC50 values of 0.43 μg/mL and 1.4 μg/mL, respectively [1].
M62812 inhibits LPS-induced NF-κB activation in HEK293 cells with an IC50 of 2.4 μg/mL. It also inhibits LPS-induced cytokine production and procoagulant effects in peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVECs). The compound suppresses the upregulation of inflammatory cytokines, adhesion molecules, and procoagulant activity in human vascular endothelial cells. |
| ln Vivo |
M62812 (iv; 10–20 mg/kg; single dose) protects against endotoxic shock in a D-galactosamine-sensitized mice model by lowering coagulation and inflammatory markers[1]. By using the mouse cecal ligation and puncture paradigm, M62812 (iv; 20 mg/kg; once daily for three days) avoids mouse death[1].
In vivo, M62812 prevents lethal septic shock in mice. By inhibiting TLR4 signaling, it suppresses endothelial cell and leukocyte activation, reduces the inflammatory response, and prevents the systemic effects of sepsis. The compound's ability to reduce LPS-induced coagulation and inflammatory responses makes it a valuable tool for studying sepsis and related inflammatory conditions. |
| Enzyme Assay |
In vitro binding and functional assays for M62812 are used to characterize its activity as a TLR4 inhibitor. NF-κB reporter assays are performed using HEK293 cells transfected with TLR4 and an NF-κB-luciferase reporter. Cells are stimulated with LPS in the presence of increasing concentrations of M62812, and inhibition of NF-κB activation is measured. The reported IC50 is 2.4 μg/mL.
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| Cell Assay |
Cellular assays for M62812 involve treating PBMCs or HUVECs with the compound and measuring inhibition of LPS-induced responses. Readouts include inhibition of pro-inflammatory cytokine production (measured by ELISA), reduction of adhesion molecule expression (measured by flow cytometry or Western blot), and inhibition of procoagulant activity. These assays confirm the compound's ability to inhibit TLR4-mediated cellular activation.
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| Animal Protocol |
Animal/Disease Models: D-galactosamine-sensitized endotoxin shock mouse model[1]
Doses: 10-20 mg/kg Route of Administration: intravenous (iv) administration (iv) Experimental Results: Prevented elevation of TNF-α, IL-6, soluble E-selectin, thrombin/ antithrombin complexes and glutamic pyruvic transaminase activity at 20 mg/kg. Prolonged survival in a d-galactosamine-sensitized endotoxin shock mouse model. Animal/Disease Models: Cecal ligation and puncture mouse model[1] Doses: 20 mg/kg Route of Administration: intravenous (iv) administration ( iv); one time/day for three days Experimental Results: decreased mortality in a murine cecal ligation and puncture model. In vivo efficacy of M62812 is evaluated in mouse models of septic shock. The compound is administered via injection, and its ability to prevent LPS-induced lethality is assessed. Efficacy endpoints include survival rates, reduction of inflammatory cytokine levels in serum, and attenuation of tissue damage. The compound's ability to suppress endothelial and leukocyte activation in vivo contributes to its protective effects against septic shock. |
| ADME/Pharmacokinetics |
M62812 has a molecular formula of C13H13Cl2N3OS (or C13H11N3OS·2HCl) and a molecular weight of 330.23. It is supplied as a solid with high purity. As a small-molecule TLR4 inhibitor, its pharmacokinetic properties would be characteristic of this class. The compound should be stored under recommended conditions. It is for research use only and is not intended for human therapeutic use.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for M62812. As a TLR4 inhibitor, its safety profile would be an important consideration for therapeutic applications. Potential toxicities could be related to its effects on innate immune responses. Standard preclinical safety studies would be required to evaluate its safety for potential therapeutic applications.
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| References | |
| Additional Infomation |
Toll-like receptor 4 signaling inhibitors can suppress endothelial cell and leukocyte activation and prevent fatal septic shock; the structure is described in the first article.
M62812 (CAS#: 613263-00-6) is a toll-like receptor 4 (TLR4) signaling inhibitor. It inhibits LPS-induced NF-κB activation in HEK293 cells with an IC50 of 2.4 μg/mL. M62812 suppresses endothelial cell and leukocyte activation and prevents lethal septic shock in mice. It has a molecular formula of C13H13Cl2N3OS and a molecular weight of 330.23. It is a research tool for studying sepsis and inflammatory diseases and is not approved for clinical use. |
| Molecular Formula |
C13H13CL2N3OS
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| Molecular Weight |
330.23
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| Exact Mass |
329.015
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| CAS # |
613263-00-6
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| Related CAS # |
M62812 free base;613262-61-6
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| PubChem CID |
44224214
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
291
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C(=C1)N)OC2=CC3=C(C=C2)C(=NS3)N.Cl.Cl
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| InChi Key |
SMTKPLISDFNJDJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H11N3OS.2ClH/c14-10-3-1-2-4-11(10)17-8-5-6-9-12(7-8)18-16-13(9)15;;/h1-7H,14H2,(H2,15,16);2*1H
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| Chemical Name |
6-(2-aminophenoxy)-1,2-benzothiazol-3-amine;dihydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
0.1 M HCL: ≥ 50 mg/mL (151.41 mM)
DMSO: 50 mg/mL (151.41 mM) H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.57 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 25.0 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 2: ≥ 2.5 mg/mL (7.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 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. View More
Solubility in Formulation 3: 2.5 mg/mL (7.57 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0282 mL | 15.1410 mL | 30.2819 mL | |
| 5 mM | 0.6056 mL | 3.0282 mL | 6.0564 mL | |
| 10 mM | 0.3028 mL | 1.5141 mL | 3.0282 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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