BT317

BT317 is a small molecule dual inhibitor of the mitochondrial protease LonP1 and the 20S proteasome. It is being developed as a therapeutic strategy for glioblastoma (GBM), specifically to address resistance to standard proteasome inhibitors like bortezomib and marizomib. LonP1 is a mitochondrial matrix protease that maintains mitochondrial proteostasis and supports metabolic reprogramming in cancer cells, serving as a key mediator of resistance to proteasome inhibition. By simultaneously targeting LonP1 and the proteasome, BT317 induces reactive oxygen species (ROS) accumulation, impairs oxidative phosphorylation, and suppresses the survival of glioma stem cells (GSCs). This dual targeting approach aims to overcome the compensatory mechanisms that allow GBM cells to survive standard proteasome inhibition, offering a potential treatment for resistant malignant glioblastoma.