CRBN versus VHL

Category:2019, News
ByUoD Web Team
On22 Feb 2019

Our new PROTAC paper on hijacking E3 ligases against each others is now published in Bioorg. Med. Chem.

Read the full paper Open Access.

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

ToC Graphic for CRBN VHL

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