A small-molecule BCL9/β-catenin blocker is tested in glioblastoma cells
- Because BCL9, a β-catenin coactivator, had lacked small-molecule inhibitors, its therapeutic value in glioblastoma had not been tested pharmacologically.
- The new inhibitor ZD37-28R was predicted by docking to bind β-catenin, and it disrupted the BCL9/β-catenin interaction in vitro.
- It suppressed β-catenin-driven transcription and reduced proliferation and migration of U87-MG and U251 glioblastoma cells.
💡 Points
Wnt/β-catenin has been a graveyard for small molecules, and a BCL9-selective PPI blocker is a more tractable angle than hitting β-catenin broadly. The open questions are the usual PPI ones: direct biophysical evidence of binding rather than docking, selectivity against other β-catenin partners, and brain exposure for a glioma indication. Treat this as target validation work, not a lead yet.