Marco Scarsi


A New Mode of Action for Sulfonylurea and Glinide Drugs: Combining Virtual Screening with Biological Assays


This work combines the predictive power of computational drug discovery with experimental validation by means of biological assays. In this way, a new mode of action for type 2 diabetes drugs is unvealed. Most drugs currently employed in the treatment of type 2 diabetes either target the sulfonylurea receptor stimulating insulin release (sulfonylureas, glinides), or target PPARgamma improving insulin resistance (thiazolidinediones).


Our work shows that sulfonylureas and glinides bind to PPARgamma and exhibit PPARgamma agonistic activity. This was predicted in silico by virtual screening and confirmed in vitro by three biological assays. This dual mode of action of sulfonylureas and glinides may open new perspectives for the molecular pharmacology of antidiabetic drugs, since it provides evidence that drugs can be designed which target both the sulfonylurea receptor and PPARgamma.


Targeting both receptors could in principle allow to increase pancreatic insulin secretion, as well as to improve insulin resistance.