Dual Targeting of DNA and EGFR by ZYH005 Induces DNA Damage and Mitotic Catastrophe in Glioblastoma - PubMed
6 hours ago
- #DNA damage
- #EGFR inhibition
- #Glioblastoma
- ZYH005 (Z5) is a brain-penetrant DNA intercalator with low systemic toxicity that shows potent anti-proliferative effects on glioblastoma (GBM) cells and stem cells, and suppresses tumor growth in mouse models.
- Z5 exerts anti-GBM activity through a dual mechanism: DNA intercalation causing DNA damage and targeted inhibition of EGFR at E762, disrupting nuclear EGFR-WEE1 interaction and impairing G2/M checkpoint.
- Extranuclearly, Z5 inhibits canonical EGFR downstream pathways (mTOR and ERK), leading to cell cycle arrest and mitotic catastrophe, overcoming limitations of single-target therapies.
- This study establishes Z5 as a promising clinical candidate for classical GBM by synergistically targeting both DNA and EGFR, advancing understanding of EGFR-WEE1 biology.