ONC-127

ONC-127 is a small molecule imipridone derivative developed by Oncoceutics (now a subsidiary of Chimerix). It belongs to a class of compounds designed to target mitochondrial proteostasis in cancer cells. Specifically, ONC-127 acts as a potent allosteric activator of the mitochondrial Caseinolytic protease P (ClpP). By binding to and hyperactivating ClpP, the drug induces the uncontrolled degradation of essential mitochondrial proteins, particularly those involved in the electron transport chain and metabolic pathways. This leads to mitochondrial dysfunction, inhibition of oxidative phosphorylation, and subsequent apoptosis. While related to the more clinically advanced imipridones ONC-201 and ONC-206, ONC-127 is primarily utilized in research to explore the therapeutic potential of ClpP activation in various solid and hematological malignancies.