| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
NOD2
As a synthetic analog of MDP, Mifamurtide is a specific ligand for the NOD2 (nucleotide-binding oligomerization domain-containing protein 2) receptor, which is an intracellular pattern recognition receptor. By activating NOD2, it triggers a signaling cascade that enhances the production of pro-inflammatory cytokines, leading to the activation of macrophages and monocytes. |
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| ln Vitro |
MG63 cell count is lowered when co-cultured with macrophages using Mifamurtide TFA (MTP-PE TFA; 100 µM)[3]. A 100 µM dose of mifamurtide TFA enhances the pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines, iNOS and CD206 mRNAs, which are markers of M1 and M2 polarization, respectively. DMT1, the iron transporter protein, is upregulated by mifamurtide TFA[3]. The growth rate of the two osteosarcoma cell lines, MOS-J and KHOS, in vitro and in vivo, is not directly impacted by L-mifamurtide TFA(5, 5000 nM; for 48 hours)[1]. TNF-a, interleukin (IL)-1, IL-6, IL-8, IL-12, nitric oxide (NO), prostaglandin E2 (PGE2), and PGD2 are among the pro-inflammatory cytokines secreted by macrophages and monocytes that are activated by mifamurtide TFA and are linked to the upregulation of tumoricidal activity [3].
Mifamurtide TFA (100 uM) induces a phenotypic shift in tumor-associated macrophages (TAMs), characterized by the upregulation of both M1 (iNOS) and M2 (CD206) polarization markers. It increases the secretion of pro-inflammatory (IL-1beta, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines, and upregulates the iron transporter protein DMT1. At a dose of 100 uM, it reduces the number of MG63 osteosarcoma cells when co-cultured with macrophages. |
| ln Vivo |
The administration of Mifamurtide TFA (MTP-PE TFA; 1 mg/kg; iv; twice weekly for 4 weeks) results in a decreased tendency of spontaneous lung metastasis proliferation[1]. In mice with endotoxemia, mifamurtide TFA (50 μg/mouse) enhances glucose tolerance. In HFD-fed rats, mifamurtide TFA (equal to 20 μg MDP; administered four times a week for five weeks) increases glucose tolerance without changing body mass[2].
Not available. In vivo, the compound does not directly impact the growth rate of osteosarcoma cell lines (MOS-J, KHOS) in vitro or in vivo. However, its immunomodulatory activity leads to a decreased tendency of spontaneous lung metastasis proliferation. It also improves glucose tolerance during endotoxemia in mice and in high-fat diet-fed mice without affecting body mass. |
| Enzyme Assay |
A standard assay for assessing NOD2 activation involves using HEK293T cells transfected with a NOD2 expression plasmid and an NF-kappaB luciferase reporter. The cells are treated with varying concentrations of Mifamurtide TFA for 6-8 hours. After treatment, cell lysates are prepared, and luciferase activity is measured. An increase in luminescence indicates NOD2 activation.
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| Cell Assay |
For assessing the activity of an immunomodulator like Mifamurtide, human peripheral blood mononuclear cells (PBMCs) are isolated and cultured in the presence of various concentrations of the compound. After a defined period (e.g., 24-48 hours), the cell culture supernatant is collected, and the levels of key cytokines like TNF-alpha, IL-1beta, IL-6, and IL-10 are quantified by ELISA.
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| Animal Protocol |
Animal/Disease Models: C57BL/6, balb/c (Bagg ALBino) mouse with KHOS osteosarcoma cells[ 1]
Doses: 1 mg/kg Route of Administration: IV; twice per week for 4 weeks Experimental Results: Caused a trend of diminished spontaneous lung metastasis dissemination in xenogeneic (KHOS) and syngeneic (MOS-J) models. In a typical in vivo study, Mifamurtide TFA is administered intravenously (e.g., at 1 mg/kg) twice weekly for 4 weeks to mice with established tumors. Tumor growth and spontaneous metastasis are monitored. For glucose tolerance studies, the compound is administered to mice, followed by an intraperitoneal glucose tolerance test (IPGTT). Blood glucose levels are measured at various time points after a glucose load. |
| ADME/Pharmacokinetics |
As a lipophilic muramyl peptide, Mifamurtide TFA would have a short plasma half-life if administered systemically, but it is designed to be encapsulated in liposomes (MTP-PE). This liposomal formulation (Mepact) targets the drug to macrophages, which are abundant in the liver, spleen, and lungs, giving it a prolonged pharmacological effect.
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| Toxicity/Toxicokinetics |
The primary toxicity associated with Mifamurtide is an intense, transient immune-mediated response, including flu-like symptoms, which is a direct extension of its mechanism of action. Studies with the cAC10-L1-MMAF4 ADC showed MTDs of 50 mg/kg in mice and 15 mg/kg in rats. Chronic use could potentially lead to chronic inflammation.
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| References |
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| Additional Infomation |
In clinical terms, Mifamurtide (as Mepact) is an orphan drug that has been approved for the treatment of high-grade, resectable, non-metastatic osteosarcoma. It is typically used in combination with standard chemotherapy after surgical resection to improve survival. This is a significant distinction: while not approved for in vitro research, the TFA salt form of the drug, like the clinically approved sodium salt (Mepact), is a potent research tool. However, **this product is strictly for laboratory research use.**
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| Molecular Formula |
C61H110F3N6O21P
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|---|---|
| Related CAS # |
Mifamurtide;83461-56-7;Mifamurtide sodium;90825-43-7;Mifamurtide sodium hydrate;838853-48-8
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| Appearance |
Typically exists as solid at room temperature
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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 :~25 mg/mL (~18.50 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.) |
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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