Recent developments in ITC instrumentation,  have led to an increase in the throughput and decrease in the protein consumption of the technique. In addition, there have been recent methodological advancements that have extended the affinity range that ITC can measure into the mM range.  The combination of all these factors has made the technique ideal for fragment based drug discovery campaigns.

This work outlines the role of an automated MicroCal ITC system in the fragment based drug discovery program of Sprint Bioscience, to identify and optimize potential drug candidates that will inhibit the activity of Vps34. This class 3 phosphatidylinositol 3-kinase is central to autophagy and has been shown to play an important role in resistance to cancer drugs^2,3. As such it has been identified as a target for therapeutic intervention.

ITC is a generic assay without the need for assay development and as such the affinity of all 50 compounds was measured in less than three days after receiving the purified protein. This approach was fast and proved very successful for identifying fragments that co-crystallized with the target protein. Of the 14 compounds chosen, based on the ITC data,12 formed crystals that could be used in the optimization process.