RGS proteins represent a novel family of proteins that regulate the activity of G protein and G protein-coupled receptors. There are over twenty members of this protein family, and it continues to grow as new members are discovered. The primary action of RGS proteins is to speed the deactivation of G proteins thus inhibiting G protein signaling. G protein-coupled receptors are involved in many diseases, but are also the target of around half of all modern medicinal drugs. RGS proteins represent a novel drug target such that inhibitors can increase signaling by endogenous hormones and neurotransmitters or may improve the specificity of existing agonist drugs.
University of Michigan researchers have discovered a series of compounds that show inhibitory activity at several different RGS proteins. They also describe the specificity for different RGS proteins and structure-activity relations for the series of compounds. The researchers have also identified methods of using such inhibitors to modulate physiological effects of G protein signaling. Since there are no known RGS inhibitors, these new compositions provide lead compounds for the development of more potent and specific RGS inhibitors. Also, the site with which the compound interacts should serve as a novel target for drug action.
Applications and Advantages
- Novel inhibition of RGS proteins involved in G protein signaling.
- Specific interaction with RGS protein that should also provide novel drug targets.