| Size | Price | Stock | Qty |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 1g |
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| Other Sizes |
Purity: ≥98%
| Targets |
Toll-like receptor 4 (TLR4) - inhibits signaling in enterocytes and macrophages.
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| ln Vitro |
In vitro studies demonstrate that TLR4-IN-C34 is an inhibitor of TLR4 signaling, a key pattern recognition receptor that recognizes bacterial lipopolysaccharide (LPS) and initiates pro-inflammatory responses. The compound inhibits TLR4 in enterocytes and macrophages when used at 10 µM, and does not affect signaling through either TLR2 or TLR9, indicating selectivity for TLR4. By inhibiting TLR4, the compound blocks the downstream signaling pathways that lead to the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. TLR4-IN-C34 has been used as an inhibitor in high-fat diet-feeding mice to verify in vitro pathways involving stearic acid, lactate dehydrogenase (LDH), and cytokines in vivo.
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| ln Vivo |
TLR4-IN-C34 (C34, orally administered once daily at a dose of 1 mg/kg) has been shown to significantly protect the intestinal mucosa and lessen the severity of NEC [1].
In vivo studies have demonstrated that TLR4-IN-C34 is an orally active TLR4 inhibitor that reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. In the endotoxemia model, administration of the compound reduces the inflammatory response to LPS challenge, as measured by decreased levels of pro-inflammatory cytokines. In the necrotizing enterocolitis model, a severe inflammatory disease of the newborn intestine, TLR4-IN-C34 reduces intestinal inflammation and tissue damage. These findings support the potential of TLR4-IN-C34 as a therapeutic agent for various inflammatory conditions including sepsis, autoimmune disorders, and chronic inflammatory diseases. |
| Enzyme Assay |
For TLR4 signaling inhibition studies, cell-based assays are performed using cells that express TLR4 such as macrophages (e.g., RAW 264.7) or intestinal epithelial cells. Cells are treated with TLR4-IN-C34 at varying concentrations and then stimulated with LPS (a TLR4 agonist). TLR4 activation is assessed by measuring the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) by ELISA or by measuring NF-κB activation using a luciferase reporter assay. The IC50 for inhibition of cytokine production or NF-κB activation is calculated from dose-response curves. Selectivity over TLR2 and TLR9 is confirmed using similar assay formats with the appropriate agonists.
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| Cell Assay |
Cellular assays for TLR4-IN-C34 typically involve culturing macrophages (RAW 264.7, THP-1) or intestinal epithelial cells and treating them with the compound at various concentrations. Cells are stimulated with LPS (from E. coli) to activate TLR4 signaling, and the production of pro-inflammatory cytokines is measured by ELISA or multiplex bead-based assays. NF-κB activation is assessed by Western blotting for phosphorylated IκBα or p65, or by using NF-κB luciferase reporter cell lines. The compound's ability to inhibit TLR4-mediated inflammatory responses is quantified, and IC50 values are calculated. Cytotoxicity against mammalian cells is assessed in parallel to evaluate selectivity.
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| Animal Protocol |
Animal/Disease Models: Experimental NEC induction in 7-8 day-old mice [1].
Doses: 1 mg/kg. Doses: Take orally every morning Experimental Results: diminished intestinal inflammation. In vivo efficacy of TLR4-IN-C34 is evaluated in mouse models of endotoxemia and necrotizing enterocolitis. For endotoxemia studies, mice are treated with the compound via oral administration prior to or following LPS injection. Serum cytokine levels are measured by ELISA, and tissue inflammation is assessed by histopathological examination. For necrotizing enterocolitis studies, mice (often neonatal mice) are subjected to conditions that induce the disease (e.g., formula feeding, hypoxia, and LPS exposure), and then treated with TLR4-IN-C34. Intestinal inflammation, tissue damage, and survival are assessed. The compound has also been used in high-fat diet-fed mice to verify in vitro pathways in vivo. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of TLR4-IN-C34 have been characterized to support its use as an orally active research tool. The compound's molecular weight of 389.4 and chemical properties influence its absorption, distribution, metabolism, and excretion (ADME) characteristics. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and tissue samples following administration. The compound's ability to reach the gastrointestinal tract and systemic circulation is important for its efficacy in models of inflammatory diseases. The compound's oral bioavailability supports its use in chronic inflammatory disease models.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of TLR4-IN-C34 is typically conducted in parallel with efficacy studies in animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of mammalian cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs and body weight changes, and histopathological examination of major organs. As a TLR4 inhibitor, potential effects on the immune system's ability to respond to bacterial infections are carefully monitored. The compound's safety profile is established to define the therapeutic window for research applications.
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| References |
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| Additional Infomation |
TLR4-IN-C34 is a research tool compound used for studying TLR4-mediated inflammatory responses and for exploring therapeutic approaches to inflammatory diseases. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves inhibition of TLR4 signaling in enterocytes and macrophages, which blocks the production of pro-inflammatory cytokines in response to LPS and other TLR4 agonists. The compound's selectivity for TLR4 over TLR2 and TLR9 makes it valuable for dissecting the specific role of TLR4 in inflammatory diseases. TLR4-IN-C34 has been used to investigate the role of TLR4 in various conditions including sepsis, necrotizing enterocolitis, and metabolic inflammation associated with high-fat diet.
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| Molecular Formula |
C17H27NO9
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| Molecular Weight |
389.397586107254
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| Exact Mass |
389.168
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| Elemental Analysis |
C, 52.44 H, 6.99 N, 3.60 O, 36.98
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| CAS # |
40592-88-9
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| PubChem CID |
91691128
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
519.8±50.0 °C at 760 mmHg
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| Flash Point |
268.2±30.1 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.484
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| LogP |
0.83
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
27
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| Complexity |
563
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O1[C@@H]([C@@H]([C@H]([C@@H]([C@H]1COC(C)=O)OC(C)=O)OC(C)=O)NC(C)=O)OC(C)C
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| InChi Key |
KMIQMFHPUJUDMC-HHARLNAUSA-N
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| InChi Code |
InChI=1S/C17H27NO9/c1-8(2)24-17-14(18-9(3)19)16(26-12(6)22)15(25-11(5)21)13(27-17)7-23-10(4)20/h8,13-17H,7H2,1-6H3,(H,18,19)/t13-,14-,15-,16-,17+/m1/s1
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| Chemical Name |
[(2R,3S,4R,5R,6S)-5-acetamido-3,4-diacetyloxy-6-propan-2-yloxyoxan-2-yl]methyl acetate
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| Synonyms |
TLR4-C34; TLR4-C-34; TLR4-C 34; C34; C 34; C-34; TLR4-IN-C34; Toll-Like Receptor 4-C34;
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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 : ~250 mg/mL (~642.01 mM)
H2O : ~33.33 mg/mL (~85.59 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (16.05 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 62.5 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 2: ≥ 6.25 mg/mL (16.05 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 62.5 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. View More
Solubility in Formulation 3: ≥ 6.25 mg/mL (16.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 7.69 mg/mL (19.75 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5681 mL | 12.8403 mL | 25.6805 mL | |
| 5 mM | 0.5136 mL | 2.5681 mL | 5.1361 mL | |
| 10 mM | 0.2568 mL | 1.2840 mL | 2.5681 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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