An image of ClpP activated by ONC201.

ClpP activated by ONC201

The crystal structure of ClpP protease activated by the experimental Phase 2 anti-cancer drug ONC 201, as determined by graduate student Ondrej Halgas in Emil F. Pai’s lab, was featured on the cover of the current issue (May 13th, 2019) of the journal Cancer Cell. Together with the laboratories of Walid Houry, Aaron Schimmer (Medical Biophysics) and Michael Andreeff (MD Anderson, Texas), they identified ClpP as the first confirmed molecular target of ONC201 with functional importance for its cytotoxicity. By combining the expertise of the various laboratories’, they showed that ONC201 binds with high affinity to ClpP and induces ClpX-independent activation resulting in the degradation of respiratory chain subunits in cancer cells. This study illustrates that mitochondrial dysregulation may be an attractive new strategy in cancer therapy.

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