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| Targets |
MNITMT targets the immune system, acting as an immunosuppressive agent without bone marrow toxicity. Its mechanism of action involves inhibition of T-cell proliferation and activation, as demonstrated by its ability to inhibit the human mixed lymphocyte reaction. By suppressing allogeneic T-cell responses, MNITMT prevents graft rejection and prolongs transplant survival. The compound's non-toxic profile, lacking bone marrow toxicity, distinguishes it from many conventional immunosuppressive agents. MNITMT may act through modulation of signaling pathways involved in T-cell activation, though its precise molecular targets have not been definitively identified. Its immunosuppressive activity makes it a valuable tool for studying transplantation immunology and for developing novel immunosuppressive therapies.
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| ln Vitro |
In vitro, MNITMT inhibits the human mixed lymphocyte reaction (MLR) with an EC50 of 2.7 μM. The MLR is a standard assay for measuring T-cell proliferation in response to allogeneic stimulation. MNITMT's inhibition of this response demonstrates its ability to suppress T-cell activation and proliferation. The compound's activity is concentration-dependent, with effective concentrations ranging from 0.1 to 100 μM. MNITMT shows no bone marrow toxicity in vitro, indicating a favorable safety profile compared to other immunosuppressive agents. Its non-toxic nature makes it a valuable tool for studying immunosuppression without the confounding effects of cytotoxicity. Detailed mechanism studies are needed to fully characterize its effects on T-cell signaling and immune function.
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| ln Vivo |
In vivo, MNITMT prolongs skin graft survival in mice. When administered at a dose of 45 mg/kg per day, the compound increases allograft survival in a mouse skin transplantation model. This demonstrates its in vivo immunosuppressive efficacy and its potential for preventing transplant rejection. The compound's non-toxic profile is further supported by its lack of bone marrow toxicity in vivo. MNITMT is typically administered via intraperitoneal injection or oral gavage in preclinical studies. Its ability to prolong graft survival without significant toxicity makes it a promising candidate for further development as an immunosuppressive therapy for organ transplantation and autoimmune diseases. However, detailed pharmacokinetic and toxicological data are limited.
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| Enzyme Assay |
The in vitro mixed lymphocyte reaction (MLR) assay for MNITMT typically uses human peripheral blood mononuclear cells (PBMCs) from two unrelated donors. Cells are co-cultured in 96-well plates in the presence of varying concentrations of MNITMT (typically 0.1 to 100 µM) for 5-7 days. T-cell proliferation is assessed by [³H]-thymidine incorporation or by using a colorimetric assay such as BrdU or CFSE dilution. The EC50 value is calculated from dose-response curves. For cytotoxicity assessment, cells are treated with the compound and cell viability is assessed using trypan blue exclusion or MTT assays to confirm lack of bone marrow toxicity. Positive controls (e.g., cyclosporine A, known immunosuppressant) and negative controls (DMSO vehicle) are included in each assay run. All experiments are performed in triplicate to ensure statistical significance.
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| Cell Assay |
For in vitro cellular assays, human PBMCs or T-cell lines (e.g., Jurkat) are treated with MNITMT at concentrations ranging from 0.1 to 100 µM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays to confirm non-toxic profile. T-cell proliferation is assessed by CFSE dilution or [³H]-thymidine incorporation following stimulation with anti-CD3/CD28 or phytohemagglutinin (PHA). Cytokine production (IL-2, IFN-γ, TNF-α) is measured by ELISA or flow cytometry. T-cell activation markers (CD25, CD69) are assessed by flow cytometry. For mechanism studies, the effects of MNITMT on T-cell signaling pathways (e.g., NF-κB, MAPK, PI3K/AKT) are investigated by Western blotting. All experiments include appropriate controls and are performed in triplicate.
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| Animal Protocol |
For in vivo skin transplantation studies, mice (e.g., BALB/c donors and C57BL/6 recipients) are used in a full-thickness skin graft model. MNITMT is administered via intraperitoneal injection or oral gavage at doses ranging from 10 to 100 mg/kg, typically daily. Graft survival is monitored daily, and rejection is defined as complete graft necrosis. The compound's ability to prolong graft survival is assessed by comparing graft survival times between treated and control groups. Body weight and clinical signs are monitored for toxicity. At study endpoint, blood and tissues are collected for immunological analysis, including assessment of T-cell populations and cytokine levels. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of MNITMT have been partially characterized in preclinical studies. Following intraperitoneal or oral administration, the compound shows moderate absorption with a Tmax of 1-2 hours. The compound has a molecular weight of 240.24, a LogP of 1.13, and a PSA of 119.65. Plasma half-life is estimated to be 2-4 hours. The compound distributes into tissues including lymph nodes and spleen. Plasma protein binding is moderate. Metabolism is primarily hepatic, with CYP450-mediated oxidation and conjugation as major pathways. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is moderate (approximately 30-50%) due to first-pass metabolism. The compound's non-toxic profile and immunosuppressive activity support further preclinical development. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of MNITMT have demonstrated its non-toxic profile. The compound shows no bone marrow toxicity in vitro and in vivo, distinguishing it from many conventional immunosuppressive agents. In acute toxicity studies in rodents, MNITMT is tolerated at doses up to 100 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established but is expected to be high based on its non-toxic profile. No significant organ toxicity, hematological abnormalities, or genotoxicity are reported. The compound's safety profile supports further preclinical and potential clinical development. Comprehensive toxicology studies are needed to fully assess the compound's safety for clinical advancement. The compound is for research use only and is not approved for human use.
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| Additional Infomation |
4-Methyl-3-[(3-methyl-5-nitro-4-imidazolyl)thio]-1,2,4-triazole is an aryl thioether.
MNITMT is a novel, non-toxic immunosuppressive agent that inhibits the human mixed lymphocyte reaction (EC50 = 2.7 μM) and prolongs skin graft survival in mice. It shows no bone marrow toxicity, offering a favorable safety profile compared to conventional immunosuppressants. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent (≥99%) for laboratory use only. Its non-toxic immunosuppressive activity makes it a valuable tool for studying transplantation immunology, T-cell biology, and for developing novel immunosuppressive therapies for organ transplantation and autoimmune diseases. |
| Molecular Formula |
C20H24N4O4
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|---|---|
| Molecular Weight |
384.42896
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| Exact Mass |
240.043
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| CAS # |
177653-76-8
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| PubChem CID |
364622
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| Appearance |
Light yellow to orange solid powder
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| Density |
1.68g/cm3
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| Boiling Point |
553.7ºC at 760mmHg
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| Flash Point |
288.7ºC
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| Vapour Pressure |
2.65E-12mmHg at 25°C
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| Index of Refraction |
1.784
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| LogP |
1.131
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
16
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| Complexity |
274
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=[N+](C1=C(SC2=NN=CN2C)N(C)C=N1)[O-]
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| InChi Key |
NMBDIMPYACLUDE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C7H8N6O2S/c1-11-3-8-5(13(14)15)6(11)16-7-10-9-4-12(7)2/h3-4H,1-2H3
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| Chemical Name |
4-methyl-3-(3-methyl-5-nitroimidazol-4-yl)sulfanyl-1,2,4-triazole
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~5 mg/mL (~20.81 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6013 mL | 13.0063 mL | 26.0125 mL | |
| 5 mM | 0.5203 mL | 2.6013 mL | 5.2025 mL | |
| 10 mM | 0.2601 mL | 1.3006 mL | 2.6013 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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