ONC206

ONC206 is an orally available, second-generation small molecule imipridone developed as a dual-targeted investigational therapy for oncology. It acts as an agonist of the mitochondrial protease ClpP (caseinolytic peptidase P) and an antagonist of the dopamine D2 receptor (DRD2). ONC206 induces a stress response in tumor cells, leading to apoptosis without affecting normal cells. Its mechanism involves activation of the integrated stress response (ISR), alteration of mitochondrial bioenergetics, inhibition of pro-survival Ras signaling pathways, and suppression of AKT/ERK signaling. Preclinical studies have shown that ONC206 is more potent than its predecessor ONC201 in killing cancer cells and has demonstrated efficacy across various difficult-to-treat central nervous system (CNS) tumors such as high-grade glioma and medulloblastoma, as well as non-CNS solid tumors including neuroendocrine tumors, breast cancer, endometrial cancer, ovarian cancer, liver cancer, triple negative breast cancer, melanoma, colorectal cancer. The drug is administered orally and has good CNS penetration[3][4][5][6][7][8].

Other names

imipridone derivativebenzyl-flurobenzyl imipridone