De novo designed proteins bind MYC's disordered regions and slow MYC-driven tumors
- Designed proteins target conserved epitopes in MYC, including intrinsically disordered motifs needed for its oncogenic activity.
- They bind MYC tightly in vitro; in cells they engage MYC, disrupt MAX pairing and reshape MYC-associated complexes.
- Expressing the binders curbed proliferation across several MYC-dependent hematopoietic, liver, pancreatic and patient-derived models, and depleted tumor cells in an orthotopic pancreatic model.
💡 Points
MYC has no pocket for a small molecule to sit in, so going after disordered epitopes with designed binders is a sensible way around that. For us it's a target-validation tool first: expression inside the cell says nothing about delivery, and a protein binder won't become a drug without a delivery story. Still, it shows where a small-molecule PPI or degrader program should aim.