The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia.
Yongwei SuJenna L CarterXinyu LiYu FukudaAshley GrayJohn LynchHolly EdwardsJun MaPatrick A SchreinerLisa PolinJuiwanna KushnerSijana H DzinicSteven A BuckShondra M Pruett-MillerKatie Hege HurrishCamenzind G RobinsonXinan QiaoShuang LiuShuangshuang WuGuan WangJing LiJoshua E AllenVarun V PrabhuAaron David SchimmerDhananjay JoshiShiva Kalhor-MonfaredIain D G WatsonRichard MarcellusMethvin B IsaacRima Al-AwarJeffrey W TaubHai LinJohn D SchuetzYubin GePublished in: Cancer research (2024)
In AML cells, ONC213 suppresses αKGDH, which induces a unique mitochondrial stress response, and reduces MCL1 to decrease oxidative phosphorylation and elicit potent antileukemia activity. See related commentary by Boët and Sarry, p. 950.