MitoBloCK-10

MitoBloCK-10 is an inhibitor of mitochondrial protein import.¹ It inhibits the import of cytochrome c1 into the mitochondrial intermembrane space in yeast cells when used at a concentration of 100 µM. MitoBloCK-10 (25 µM) inhibits migration and invasion of, and induces apoptosis and cell cycle arrest at the G₁ phase in, primary human bladder cancer cells.² It induces mitochondrial depolarization, decreases ATP levels, and increases reactive oxygen species (ROS) in primary human bladder cancer cells. MitoBloCK-10 (20 mg/kg every other day) decreases tumor volume in a patient-derived xenograft (PDX) mouse model of bladder cancer. Intravitreal administration of MitoBloCK-10 (0.25 nM/eye) reduces superoxide dismutase (SOD) activity and increases TBARS levels and acellular capillary numbers in mouse retina.³ It induces dorsal curvature and cardiac apoptosis in zebrafish embryos when used at a concentration of 10 µM.¹

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1. Miyata, N., Tang, Z., Conti, M.A., et al. Adaptation of a genetic screen reveals an inhibitor for mitochondrial protein import component Tim44. The Journal of Biological Chemisty 292(13), 5429-5442 (2017).

2. Zhang, L., Shi, X., Zhang, L., et al. A first-in-class TIMM44 blocker inhibits bladder cancer cell growth. Cell Death Dis. 15(3), 204 (2024).

3. Ma, Z.-R., Li, h.-P., Cai, S.-Z., et al. The mitochondrial protein TIMM44 is required for angiogenesis in vitro and in vivo. Cell Death Dis. 14(5), 307 (2023).