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DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells

Citation:
Sterling JR, Holtsmark JR, ……. Kuchibhotla M, Johns TG, deWeck A, et al. DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells. Nat Chem Biol. 2026. 

Keywords:
Children's cancers; glioblastoma; chemical biology; therapeutic targets

Abstract:
Histone lysine demethylase 4 (KDM4) enzymes are frequently overexpressed in cancer and are considered to be promising therapeutic targets. QC6352, which is widely used as a best-in-class KDM4 chemical probe, shows potent antitumor activity across cancer models. Using comprehensive chemical biology approaches in glioblastoma models, we demonstrate that the efficacy of QC6352 and that of its clinical analog zavondemstat are independent of KDM4 inhibition.