ONC-201

ONC-201 is an orally active transcriptional inducer of Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). It induces TRAIL in a p53-independent manner at concentrations of 1.25 μM-5 μM and crosses the blood-brain barrier. It inactivates kinases Akt and extracellular signal–regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. It causes tumor regression in HCT116 p53−/− xenograft bearing mice.