| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
ST-2825 targets MyD88 (myeloid differentiation primary response 88), an essential adaptor protein in the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways. MyD88 is recruited to the receptor complex upon ligand binding and undergoes dimerization. This dimerization is required for the recruitment of IRAK1 and IRAK4, which then activate downstream signaling cascades, including the NF-κB and MAPK pathways, leading to the production of pro-inflammatory cytokines. ST-2825 inhibits MyD88 dimerization, thereby blocking the recruitment of IRAK1 and IRAK4 and preventing the activation of NF-κB. This results in the inhibition of IL-1β-mediated inflammatory responses. By targeting this key adaptor protein, ST-2825 modulates a wide range of innate immune responses.
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| ln Vitro |
IL-1R/TLR signaling is inhibited by ST2825 through disruption of MyD88 homodimerization. The inhibition of dimerization by ST2825 is concentration-dependent, with an estimated 40% inhibition at 5 μM and an approximate 80% inhibition at 10 μM [1].
In vitro studies have demonstrated that ST-2825 is a potent inhibitor of MyD88 dimerization. The inhibition of dimerization by ST-2825 is concentration-dependent, with an estimated 40% inhibition at 5 μM and an approximate 80% inhibition at 10 μM. ST-2825 interferes with the recruitment of IRAK1 and IRAK4 by MyD88, causing inhibition of IL-1β-mediated activation of NF-κB transcriptional activity. In cell-based assays, ST-2825 significantly inhibits the proliferation of and promotes the apoptosis of hepatocellular carcinoma (HCC) cells. It significantly decreases bcl-2 expression, increases cleaved caspase-3 expression, and reduces p65 nuclear expression in a dose-dependent manner. These findings establish ST-2825 as a valuable tool for studying MyD88-mediated signaling in cancer and inflammation. |
| ln Vivo |
ST2825 significantly inhibits IL-1β-stimulated IL-6 production at concentrations of 100 and 200 mg/kg [1]. After oral administration, ST2825 dose-dependently inhibited IL-1β-induced IL-6 production in treated mice. Animals were dosed orally with appropriate vehicle or ST2825 at doses of 50 to 200 mg/kg 5 min before intraperitoneal injection of 20 μg/kg IL-1β.
In vivo studies have demonstrated that ST-2825 provides neuroprotection after experimental traumatic brain injury in mice. It significantly inhibits IL-1β-stimulated IL-6 production at concentrations of 100 and 200 mg/kg. After oral administration, ST-2825 dose-dependently inhibited IL-1β-induced IL-6 production in treated mice. Animals were dosed orally with vehicle or ST-2825 at doses of 50 to 200 mg/kg 5 minutes before intraperitoneal injection of 20 μg/kg IL-1β. These studies demonstrate the in vivo efficacy of ST-2825 in inhibiting IL-1β-mediated inflammatory responses and provide evidence for its neuroprotective effects. |
| Enzyme Assay |
The in vitro assays for ST-2825 measure its inhibition of MyD88 dimerization. MyD88 dimerization can be measured using various biochemical techniques, such as crosslinking assays, co-immunoprecipitation, or fluorescence resonance energy transfer (FRET). In a typical assay, MyD88 protein is incubated in the presence of varying concentrations of ST-2825, and the extent of dimerization is measured. Alternatively, cell-based assays using reporter genes can measure the inhibition of NF-κB transcriptional activity. In these assays, cells are transfected with an NF-κB-luciferase reporter plasmid and stimulated with IL-1β in the presence or absence of ST-2825. The inhibition of luciferase activity is measured, and the IC50 is determined. These assays provide a quantitative measure of ST-2825's potency at inhibiting MyD88-mediated signaling.
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| Cell Assay |
In vitro cell-based assays for ST-2825 are used to study its effects on MyD88-mediated signaling and cancer cell biology. A common assay involves treating hepatocellular carcinoma (HCC) cells with varying concentrations of ST-2825. Cell proliferation is assessed using assays such as MTT or CellTiter-Glo. Apoptosis is measured using Annexin V staining or caspase-3/7 activation assays. The expression of apoptosis-related proteins, such as bcl-2 and cleaved caspase-3, is assessed by Western blotting. NF-κB activation is measured by assessing the nuclear translocation of p65 or by using an NF-κB-luciferase reporter assay. These cell-based assays confirm that ST-2825 inhibits MyD88-mediated signaling and exerts anti-cancer effects in HCC cells.
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| Animal Protocol |
In vivo animal experiments for ST-2825 have been conducted in mouse models of traumatic brain injury and IL-1β-induced inflammation. In the traumatic brain injury model, mice are subjected to controlled cortical impact, and ST-2825 is administered. Neuroprotection is assessed by measuring lesion volume, neuronal cell death, and functional outcomes. In the IL-1β-induced inflammation model, mice are dosed orally with ST-2825 at doses of 50 to 200 mg/kg 5 minutes before intraperitoneal injection of 20 μg/kg IL-1β. Blood samples are collected, and the levels of IL-6 and other cytokines are measured by ELISA. These studies demonstrate the in vivo efficacy of ST-2825 in inhibiting MyD88-mediated inflammatory responses and providing neuroprotection.
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| ADME/Pharmacokinetics |
ST-2825 has a molecular weight of 591.51 g/mol and a molecular formula of C27H28Cl2N4O5S. It is a white to off-white solid powder. The compound has a logP of 4.562, indicating moderate lipophilicity. For research use, ST-2825 is typically supplied as a powder. It is soluble in DMSO and other organic solvents. For storage, it is recommended to keep the powder at -20°C in a dry, dark environment. Pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have been studied. After oral administration, ST-2825 is absorbed and can inhibit IL-1β-induced IL-6 production in a dose-dependent manner.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for ST-2825 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. In vivo studies have used doses up to 200 mg/kg in mice without reported overt toxicity. However, comprehensive toxicological studies, including acute and chronic toxicity studies, have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed when handling ST-2825. Its use is limited to research applications and it is not intended for human or veterinary use.
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| References |
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| Additional Infomation |
ST-2825 is a research compound and is not approved for any clinical or therapeutic use. It is a novel, potent, and specific inhibitor of MyD88 dimerization. ST-2825 interferes with the recruitment of IRAK1 and IRAK4 by MyD88, causing inhibition of IL-1β-mediated activation of NF-κB transcriptional activity. It significantly inhibits the proliferation of and promotes the apoptosis of HCC cells. ST-2825 provides neuroprotection after experimental traumatic brain injury in mice. The compound is used to study MyD88-mediated signaling in inflammation, immunity, and cancer. Its mechanism of action involves inhibiting MyD88 dimerization, thereby blocking downstream signaling pathways.
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| Molecular Formula |
C27H28CL2N4O5S
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| Molecular Weight |
591.504
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| Exact Mass |
590.116
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| CAS # |
894787-30-5
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| Related CAS # |
894787-30-5;
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| PubChem CID |
24808138
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| Appearance |
White to off-white solid powder
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| LogP |
4.562
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
39
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| Complexity |
967
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C1C[C@]2(C[C@@H]3N(C2=O)[C@H](CCS3)C(=O)N)N(C1)C(=O)CC4=CC=C(C=C4)NC(=O)COC5=C(C=C(C=C5)Cl)Cl
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| InChi Key |
HBLHLJXFIPCEMW-ZJSFPPFMSA-N
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| InChi Code |
InChI=1S/C27H28Cl2N4O5S/c28-17-4-7-21(19(29)13-17)38-15-22(34)31-18-5-2-16(3-6-18)12-23(35)32-10-1-9-27(32)14-24-33(26(27)37)20(25(30)36)8-11-39-24/h2-7,13,20,24H,1,8-12,14-15H2,(H2,30,36)(H,31,34)/t20-,24-,27-/m1/s1
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| Chemical Name |
(4R,7R,8aR)-1'-[2-[4-[[2-(2,4-dichlorophenoxy)acetyl]amino]phenyl]acetyl]-6-oxospiro[3,4,8,8a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazine-7,2'-pyrrolidine]-4-carboxamide
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| Synonyms |
ST-2825 ST 2825 ST2825.
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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 (~169.06 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.23 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 (4.23 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6906 mL | 8.4531 mL | 16.9062 mL | |
| 5 mM | 0.3381 mL | 1.6906 mL | 3.3812 mL | |
| 10 mM | 0.1691 mL | 0.8453 mL | 1.6906 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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