ONC213

ONC213 is a **small molecule imipridone** that acts as a potent, selective **inhibitor of alpha-ketoglutarate dehydrogenase (αKGDH)**, a key enzyme in the citric acid (TCA) cycle. This drug induces **mitochondrial stress and suppresses oxidative phosphorylation** in acute myeloid leukemia (AML) cells, leading to cell death predominantly in AML cells and leukemia stem cells, with minimal toxicity to normal hematopoietic cells[1][3][5][7][8]. ONC213 induces a unique mitochondrial stress response that reduces the translation of the anti-apoptotic protein **MCL1** and suppresses de novo protein synthesis, contributing to its antileukemic activity[3][5][7]. It does not activate the TRAIL or death receptor 5 (DR5) pathways, which distinguishes it mechanistically from its close analogue, ONC201[1][7]. The drug shows promising results both in vitro and in xenograft mouse models of AML, including those resistant to venetoclax-based therapy. ONC213 is being investigated primarily for the treatment of **acute myeloid leukemia** and acts synergistically with drugs such as venetoclax against AML[1][2][6].

Other names

ONC213ONC-213ONC 213