Researchers led by Georg Winter and collaborators used a systematic ligand‑diversification strategy combined with live‑cell functional screening to identify new molecular glues that induce targeted protein degradation. The work, published in Nature Chemical Biology and described by Miquel Muñoz i Ordoño and colleagues, focused on ENL, a chromatin reader protein driving certain acute leukemias, and discovered a compound that selectively triggers ENL degradation in leukemia cells. The team generated thousands of chemical variants from a starting ligand and screened them directly in cells to link chemical modifications to degradation outcomes. The identified glue acts through a cooperative mechanism to recruit cellular degradation machinery and suppress ENL‑dependent transcriptional programs, reducing growth of ENL‑dependent leukemia cells. Molecular glues are small molecules that stabilize new protein–protein interactions to drive clearance of disease proteins by the cell’s quality‑control systems.