Structure-based medicinal chemistry yields potent pan-YTHDF m6A reader ligands
- YTHDF1, YTHDF2 and YTHDF3 read m6A-modified mRNA in the cytosol, and this preprint reports a protein structure-based medicinal chemistry campaign against them.
- The aim is ligands that bind all three paralogs, rather than one reader at a time.
- Only the abstract opening was accessible, so potency and cellular data are not covered here.
💡 Points
The YTH domains' aromatic cage is a tough, charged pocket, so any structure-guided progress on it is worth tracking. A pan-paralog ligand is a sensible choice, given the redundancy among the three readers. I'd want selectivity over YTHDC1/2 and evidence of cellular target engagement before calling this a probe.