ONC212 (ONC-212) is a potent anti-cancer small molecule, activator of an orphan GPCR GPR132 and Gαq signaling.
ONC212 possesses highly increased antitumor activity compared to the first-generation compound ONC201.
ONC212 induced apoptogenic effects through the induction of an integrated stress response, and reduced MCL-1 expression.
Oral administration of ONC212 inhibited AML growth in vivo and improved overall survival in xenografted mice.
ONC212 exhibited broad-spectrum efficacy at nanomolar concentrations across solid tumors and hematological malignancies.
ONC212 impairs oxidative phosphorylation (OXPHOS) with decrease in mitochondrial-derived ATP production, mitochondrial protease ClpP was identified as an ONC212-binding target.
