Our paper disclosing structure-activity relationships leading to the potent VHL inhibitor VH298 is now published in J. Med. Chem.

  • Crystal structure of VH298 bound to VHL
  • Table of Content Graphics
  • Figure 1. Initial optimization strategy.
  • Figure 2. Biophysical characterization of inhibitor 10 binding to VBC.
  • Figure 3. Co-crystal structures of first-series inhibitors.
  • Figure 4. Cellular activity and toxicity of 10.
  • Figure 5. Second series optimization strategy.
  • Figure 6. Inhibitor 15 is not cytotoxic.
  • Figure 7. Co-crystal structures of second-series inhibitors.
  • Figure 8. Correlations between cellular activity and physicochemical parameters in vitro.
  • Figure 9. Activity in cells vs half-life dissociation from VBC protein complex.
  • Scheme 1.
  • Scheme 2.
  • Scheme 3.

Read our article Open Access here.

The article will be part of the journal Special Issue on "Inducing Protein Degradation as a New Therapeutic Strategy", edited by Prof. Craig Crews and Prof. Shameng Wang.