First-in-class METTL1 inhibitor STM9005 shows that blocking tRNA methylation can curb diverse cancers in mice
- Developed STM9005, a selective inhibitor of the tRNA methyltransferase METTL1, testing whether a tRNA-modifying enzyme can be drugged in cancer.
- In diverse cancer cell models, it slowed growth, shifted differentiation and disturbed the cell cycle, while lowering m7G on selected tRNAs and their levels, altering translation of oncogenic mRNAs.
- In several mouse models from different tissues, catalytic inhibition curbed tumours and extended survival.
💡 Points Based on the abstract
METTL1 is a SAM-dependent RNA methyltransferase, so my first worry is selectivity against the wider methyltransferase family; the paper's "selective catalytic inhibitor" claim is what I'd test first. A catalytic-dead phenocopy would matter more to me than efficacy across tissues, since it separates on-target from off-target toxicity.
Pharmacological inhibition of METTL1 as a therapy against solid and blood cancers ↗