Helix Mimetics as Inhibitors of the Interaction of the Estrogen Receptor with Coactivator Peptides

Abstract

The short and curlies: A new α-helix mimetic based on a pyridylpyridone scaffold has been developed to bind to the estrogen receptor (ER) by mimicking the key leucine side chains of coactivator LXXLL boxes (L=leucine, X=any amino acid). These inhibitors compete with coactivator peptides for the surface of the ER and act as small-molecule inhibitors of the ER–coactivator interaction.