Discovery of a VHL and HIF1α interaction inhibitor with in vivo angiogenic activity via structure-based virtual screening

Abstract

We describe herein compound 1, which is similar to many known natural products, as an inhibitor of the VHL–HIF1α interaction via structure-based virtual screening. Compound 1 disrupts VHL-mediated HIF1α degradation, leading to significantly increased VEGF expression. To our knowledge, compound 1 is a member of only the second class of small molecule inhibitors of the VHL–HIF1α interaction.