| Size | Price | Stock | Qty |
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| 1mg |
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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 |
MyD88 (TIR domain).
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|---|---|
| ln Vitro |
In vitro, TJ-M2010-5 (40 μM) suppresses MyD88 signaling in RAW 264.7 cells that respond to LPS (100 ng/mL) and MyD88 homodimerization in transfected HEK293 cells in a concentration-dependent manner [1]. Following stimulation with R848 (500 ng/mL), TJ-M2010-5 (5-30 μM) inhibits B cell growth and promotes B cell death [3].
TJ-M2010-5 binds selectively to the TIR domain of MyD88, disrupting homodimerization of MyD88, a critical step in TLR/IL-1R signaling. This leads to inhibition of downstream NF-kappaB activation and reduced production of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6). The compound has demonstrated efficacy in models of inflammation. |
| ln Vivo |
In a 10-week CAC mouse model, TJ-M2010-5 statistically significantly decreased AOM/DSS-induced colitis and completely prevented the development of CAC with less weight loss associated with it. As a result, the treated mice had a zero percent mortality rate, reduced cell proliferation, and increased cell apoptosis in colon tissue[1]. TJ-M2010-5 significantly decreased serum concentrations of IL-22 and IL-22-23, TGF-β1, and TNF-α, IL-6, G-CSF, MIP-1β, IL-11, and IL-17A in mice at 2 and 7 weeks after induction[1].
TJ-M2010-5 has been studied in models of myocardial ischemia/reperfusion injury (MIRI). In such models, administration of TJ-M2010-5 reduces infarct size, improves cardiac function, and decreases myocardial inflammation. It downregulates MyD88 expression, NF-kappaB activation, and pro-inflammatory cytokine production in the injured myocardium. |
| Enzyme Assay |
Not available. A generic MyD88 TIR domain binding assay can be used. Recombinant human MyD88 TIR domain (50-100 ng) is immobilized on a nickel-coated ELISA plate (if His-tagged). Varying concentrations of TJ-M2010-5 (0.1-100 microM) are added and incubated for 1-2 h at 25degC. Binding is detected using a specific anti-MyD88 antibody followed by HRP-conjugated secondary antibody and TMB substrate. Alternatively, surface plasmon resonance (SPR) with immobilized MyD88 TIR domain is used to measure direct binding affinity. Competition assays assess the ability of TJ-M2010-5 to disrupt MyD88 homodimerization using crosslinking or FRET-based assays.
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| Cell Assay |
Cell Viability Assay[3]
Cell Types: Purified B cells Tested Concentrations: 0 μM, 5 μM, 10 μM, 20 μM and 30 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited the viability of B cells with or without the stimulation of CD40L. Human THP-1 monocytes or RAW264.7 macrophages are seeded in 6-well plates (1×10⁶/well) in RPMI-1640 with 10% FBS. Cells are treated with TJ-M2010-5 (0.1-50 microM) for 1 h, then stimulated with LPS (100 ng/mL) to activate TLR4/MyD88 signaling. After 6-24 h, supernatants are collected for TNF-alpha, IL-1beta, and IL-6 ELISA. Cell lysates are analyzed by Western blot for MyD88 expression, IkappaBalpha phosphorylation, and NF-kappaB p65 nuclear translocation (by fractionation or immunofluorescence). NF-kappaB activity is measured using luciferase reporter assay in HEK293 cells co-transfected with NF-kappaB luciferase and MyD88 expression vectors. |
| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse (6–8 weeks old)[1]
Doses: 50 mg/kg Route of Administration: Treated ip daily beginning two days before the first dextran sodium sulfate (DSS) administration throughout a 10-week observation period. Experimental Results: Dramatically prevented inflammation/CAC-related body weight loss and mortality (0% vs 53% in the control group). In rat models of myocardial ischemia/reperfusion injury (MIRI), male Sprague-Dawley rats (200-250 g) undergo left anterior descending (LAD) coronary artery occlusion for 30-45 min followed by 2-24 h reperfusion. TJ-M2010-5 is administered intraperitoneally or intravenously (5-20 mg/kg) just before reperfusion. At the end of reperfusion, infarct size is measured by TTC staining, and cardiac function is assessed by echocardiography (ejection fraction, fractional shortening). Myocardial tissue is collected for TUNEL apoptosis assay, Western blot (MyD88, p-IkappaBalpha, NF-kappaB), and cytokine ELISA. Inflammatory cell infiltration is assessed by myeloperoxidase (MPO) assay and histology (H&E). |
| ADME/Pharmacokinetics |
No PK data reported. Generic PK for small molecule MyD88 inhibitors: male SD rats or C57BL/6 mice receive IV (5-10 mg/kg) and oral (20-50 mg/kg) administration. Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 18, 24 h. Plasma is analyzed by LC-MS/MS. PK parameters: t1/2 (2-5 h), Cmax (1-10 microM), Tmax (0.5-2 h), oral bioavailability (20-60%). Volume of distribution (Vd) may be moderate (1-2 L/kg), indicating some tissue distribution.
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| Toxicity/Toxicokinetics |
No toxicity data reported. Generic acute toxicity study: ICR mice (5/sex/group) receive single oral or i.p. doses of TJ-M2010-5 at 50, 150, 300, 600 mg/kg. Animals are observed for 14 days for mortality and clinical signs (body weight, food consumption, behavior). At termination, gross necropsy and histopathology of major organs (liver, kidney, spleen, heart, lung, brain, GI tract) are performed. Subchronic toxicity: rats receive daily doses at 10, 30, 100 mg/kg for 28 days, with assessment of hematology, serum chemistry, and histopathology. Immunotoxicity (lymphocyte subset analysis, cytokine levels) may also be evaluated due to the mechanism of action.
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| References |
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| Additional Infomation |
TJ-M2010-5 (CAS# 1357471-57-8) is a research-grade small molecule MyD88 inhibitor. It is not FDA-approved and has not entered clinical trials. The compound is primarily used in laboratory research to study the role of MyD88 in TLR-mediated inflammation, innate immunity, and ischemia-reperfusion injury. Its TIR domain binding mechanism distinguishes it from other MyD88 inhibitors that target the MyD88/IRAK interaction or IRAK4. TJ-M2010-5 is a valuable tool for validating MyD88 as a therapeutic target for inflammatory and autoimmune diseases.
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| Molecular Formula |
C23H26N4OS
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|---|---|
| Molecular Weight |
406.54
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| Exact Mass |
406.182
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| CAS # |
1357471-57-8
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| PubChem CID |
71542350
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
499
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(CCC(NC2=NC(C3=CC=CC=C3)=CS2)=O)CCN(CC2=CC=CC=C2)CC1
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| InChi Key |
DTIQJBUDKQVBLT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H26N4OS/c28-22(25-23-24-21(18-29-23)20-9-5-2-6-10-20)11-12-26-13-15-27(16-14-26)17-19-7-3-1-4-8-19/h1-10,18H,11-17H2,(H,24,25,28)
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| Chemical Name |
3-(4-benzylpiperazin-1-yl)-N-(4-phenyl-1,3-thiazol-2-yl)propanamide
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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) |
DMSO: 100 mg/mL (245.98 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.15 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 (6.15 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4598 mL | 12.2989 mL | 24.5978 mL | |
| 5 mM | 0.4920 mL | 2.4598 mL | 4.9196 mL | |
| 10 mM | 0.2460 mL | 1.2299 mL | 2.4598 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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