Identifying GPER Agonists with Superior Selectivity

SLU ID 18-010 | The Identification of Novel GPER Agonists

Background

Discovery of new G Protein Coupled-Estrogen Receptor (GPR30/GPER) ligands have been hampered by a lack of understanding of the important binding modes and interactions. The crystallized structure of GPER has yet to be achieved, thus ligand discovery has been reliant upon in silico library screenings and computational modeling.

Overview

Researchers at Saint Louis University have discovered new agonists that are relatively non-rigid whereas the the G-series contains a very rigid structure. The lack of rigidity in the new compounds may enable better probing of the binding pocket within GPER. The non-rigidity of the scaffold of these compounds has been shown to be superior to the G-series with regard to antagonists. Modification of the benzene ring alters the activity of the compounds from antagonists to agonists.

Benefits

The potential benefits of this technology include:

• Minimizing solubility limitations

• Increasing selectivity for GPER

• Increasing the number of models for which GPER ligands can be used

• Increasing the understanding of the role of GPER in various conditions

Applications

Potential applications of this technology include:

• Treating gallstone disease

• Treating breast cancer

• Treating cardiovascular disease

• Providing neuroprotection

Opportunity

Saint Louis University is seeking partners to further develop and commercialize this technology.