MB-10

MB-10 is a small molecule inhibitor of the Translocase of the Inner Membrane 23 (TIM23) complex, a critical component of the mitochondrial protein import machinery. Developed by researchers at the University Health Network and the Ontario Institute for Cancer Research, MB-10 targets the mitochondrial protein import pathway to disrupt mitohormesis—an adaptive stress response that multiple myeloma cells exploit to maintain mitochondrial fitness and avoid apoptosis. By inhibiting TIM23, MB-10 induces unmitigated mitochondrial stress, activating the mitochondrial unfolded protein response (UPR MT) and the integrated stress response (ISR), which ultimately triggers cell death. Preclinical studies have demonstrated that MB-10 is effective against multiple myeloma cell lines and primary patient samples, including those resistant to proteasome inhibitors, while showing minimal toxicity toward normal hematopoietic cells.