Drug Discovery & Development

Conference Review

Target Identification

Target-based drug discovery begins with the identification of the function of a potential therapeutic drug target and understanding its role in the disease process.  At this point, little may be known about proteins identified as potential drugable targets.  If the target is an enzyme, suspected catalytic activity needs to be determined as well as downstream substrates.  Specific assay methods will not exist, although generic catalytic activity can be ascertained by proteome- scale screens (protease, phosphatase, kinase, etc.).  Identifying small molecules that bind to target proteins may help elucidate information on their role in the biological process.

It is impossible to screen for unknown chemical reactions, but this is where Isothermal Titration Calorimetry (ITC) can play a critical role.  Since this technique measures the natural heat generated in a biomolecular reaction there is no requirement for any prior knowledge of the binding partners, substrates or other cofactors.  These same principles can be applied to a wide variety of biomolecular interactions which involve proteins, lipids, nucleic acids, small molecules, membranes and many others.

Measuring the binding energetics of potential targets along with their ligands by ITC can provide valuable information that can be used to deorphan receptors, confirming endogenous ligands and analogs and confirm targets.  Differential Scanning Calorimetry (DSC) can also be used to assess the quality of recombinantly expressed proteins.