ONC212

ONC212 is a second-generation small molecule imipridone and a fluorinated analogue of ONC201. It acts as a dual agonist of the mitochondrial protease ClpP and the G protein-coupled receptor GPR132. Through activation of these targets, ONC212 induces apoptosis via activation of the integrated stress response, alteration of mitochondrial bioenergetics, and inhibition of pro-survival Ras signaling pathways in tumor cells. It demonstrates potent preclinical efficacy across multiple solid tumors (including pancreatic cancer, melanoma, hepatocellular carcinoma) and hematological malignancies (such as leukemias), including models resistant to first-generation imipridones like ONC201. Compared to its predecessor, it is significantly more potent in inhibiting cell proliferation and inducing apoptosis at lower concentrations[1][2][4][5][6][7][9][10].

Other names

imipridone ONC212fluorinated-ONC201 analoguefluorinated-ONC-201 analoguefluorinated-ONC 201 analogue