Designed allosteric modulators for nuclear receptors; towards a new nuclear receptor pharmacology.

In this project, new ways have been found to pharmacologically modulate nuclear receptors, such as the Estrogen Receptor, with small molecules. Specifically, the conformation and interaction of these types of transcription factors with the 14-3-3 protein were examined. The protein-protein interaction between these proteins has been characterized and molecules have been developed that strengthen this interaction. Many promising molecules, molecular glues, have been tested on cellular and pathological systems, for example in breast cancer and diabetes, where they have shown very promising results and are the impetus for ongoing follow-up research.