CRBN versus VHL: our new PROTAC paper on hijacking E3 ligases against each others is now published in Bioorg. Med. Chem.

  • ToC graphics
  • Figure 1. Previously published homo-PROTACs CM11 and CC15a, which induce self-degradation of the E3 ligases VHL and CRBN, respectively.
  • Figure 2. Design of VHL-CRBN conjugates explored in this work.
  • Figure 3. Chemical structure of VHL ligands 1 and 2, and CRBN ligand 3.
  • Scheme 1. Synthesis of PROTACs 7a-b.
  • Scheme 2. Synthesis of PROTACs 14a-e.
  • Scheme 3. Synthesis of PROTACs 18a-c.
  • Scheme 4. Synthesis of PROTACs 22a-c.
  • Figure 4. Screening of VHL-CRBN hetero-PROTACs.
  • Figure 5. Compound 14a induces rapid depletion of CRBN, but not of VHL

Read the full paper Open Access here.

Well done Miriam, Chiara, Scott and Andrea on this work!