Mifamurtide sodium

Mifamurtide sodium (MTP-PE sodium), an analog of the muramyl dipeptide (MDP), is a nonspecific immunomodulator by stimulating the immune response activating macrophages and monocytes. Mifamurtide sodium, an orphan drug, is a specific ligand of NOD2 used as an insulin sensitizer. Mifamurtide sodium has the potential for osteosarcoma research[1][2][3].

Mifamurtide sodium (MTP-PE sodium; 100 µM) induces a reduction of MG63 cells number when co-cultured with macrophages[3]. Mifamurtide sodium (100 µM) increases both the M1 polarization marker iNOS and the M2 polarization marker CD206 mRNAs; both pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Mifamurtide sodium increases the iron transporter DMT1 protein[3]. L-mifamurtide sodium (5, 5000 nM; for 48 hours) alone has no direct effect on the proliferation rate of the two osteosarcoma cell lines MOS-J and KHOS in vitro or in vivo[1]. Mifamurtide sodium acts as a nonspecific immunomodulator by activating macrophages and monocytes related to the upregulation of tumoricidal activity and secretion of pro-inflammatory cytokines including tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, IL-8, IL-12, nitric oxide (NO), prostaglandin E2 (PGE2) and PGD2[3].

Mifamurtide sodium (MTP-PE sodium; 1 mg/kg; i.v.; twice per week for 4 weeks) causes a trend of diminished spontaneous lung metastasis dissemination[1]. Mifamurtide sodium (50 μg/mouse) improves glucose tolerance during endotoxemia in mice. Mifamurtide sodium (equivalent to 20 μg MDP; 4 times per week for 5 weeks) improves glucose tolerance in HFD-fed mice without altering body mass[2].

[1]. Kevin Biteau, et al. L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer. Am J Cancer Res. 2016 Feb 15;6(3):677-89.
[2]. Joseph F Cavallari, et al. Muramyl Dipeptide-Based Postbiotics Mitigate Obesity-Induced Insulin Resistance via IRF4. Cell Metab. 2017 May 2;25(5):1063-1074.e3.
[3]. Francesca Punzo, et al. Mifamurtide and TAM-like macrophages: effect on proliferation, migration and differentiation of osteosarcoma cells. Oncotarget. 2020 Feb 18;11(7):687-698.