MT-125 is a specific and well-tolerated inhibitor of non-muscle myosin IIA [Ki, NMIIA = 2.7 μM] and IIB [EC50 = 1.7 μM]. It can cross the blood-brain barrier and induces ferroptosis and DNA damage by raising reactive oxygen species (ROS) levels within tumor cells. Additionally, MT-125 enhances the PDGFR signaling pathway and is utilized in glioblastoma research.

MT-125 (5 μM, 8 hours) effectively inhibits the invasion capability of a mouse GBM cell line (MES1861) and three human GBM cell lines (187, 190, and L1). At the concentration of 5 μM over 48 hours, MT-125 causes 12%-25% multinucleation in 10 human GBM cell lines. When applied in a range of 0.1-10 μM for 96 hours, MT-125 exhibits over 90% cytotoxicity across various mouse and human GBM cell lines. Furthermore, MT-125 enhances reactive oxygen species (ROS) and lipid peroxidation levels in L1 cells. At 4 μM, MT-125 can induce ferroptosis in Trp53(‒/‒) cells, with its cytotoxicity being reversible by ferroptosis inhibitors. MT-125 at 5 μM for 48 hours significantly increases the expression of PDGFRα and activates downstream signaling pathways in Trp53(‒/‒) cells. Additionally, under the same conditions, MT-125 regulates MAPK signaling via NMIIA inhibition and shows synergistic effects with oncogenic kinase inhibitors in Trp53(‒/‒) cells.

MT-125, administered subcutaneously at 10 mg/kg daily for two weeks, exhibits low toxicity in C57BL/6 mice. At a dose of 20 mg/kg, given subcutaneously once daily for seven days, MT-125 does not induce any drug-related adverse effects or impact age-related weight changes in these mice. In repeated-dose toxicology studies, female rats tolerate MT-125 well at 7.5, 15, or 30 mg/kg, administered subcutaneously once daily for 28 days. Furthermore, MT-125 at 10 mg/kg, delivered intraperitoneally once daily for four weeks, works synergistically with carcinogenic kinase inhibitors to significantly inhibit tumor cell growth in glioblastoma-bearing C57BL/6 mice.