Glioblastoma study identifies DHODH as the main driver of QC6352 and zavondemstat activity
Published in Brain/Neurology, Drugs development & discovery, Journals.
Publication date: October 6, 2026.
A study published today in Nature Chemical Biology challenges how two cancer compounds have been interpreted. Researchers identify DHODH, an enzyme involved in pyrimidine production, as the dominant driver of QC6352 and zavondemstat activity in the glioblastoma models examined.
Both compounds inhibit KDM4 and DHODH. However, supplying uridine or expressing an inhibitor-resistant DHODH variant reversed their growth-inhibiting effects. A separate KDM4 inhibitor without DHODH activity did not reproduce those effects. The results support a different mechanistic explanation from attributing the response mainly to KDM4 inhibition.
This is preclinical evidence, not a demonstration of patient benefit in glioblastoma. The authors caution that target contributions may differ between disease contexts. The findings support reexamining experiments that relied on QC6352 and benchmarking zavondemstat development against DHODH inhibitor research.
Source: Sterling and colleagues, Nature Chemical Biology, published October 6, 2026. DOI: 10.1038/s41589-026-02306-x.