Target/s Identification Approaches – Experimental Biological Approaches

The unravelling of the human genome has not only opened a new avenue for an enhanced understanding of how a given repertoire of genetic information is able to create, maintain and regulate the physiological requirements for a living human organism but it has also defined a set of genes and their products which in case of aberrant activity, thus causing dysregulation and disease, might also be of relevance as potential drug targets. The challenge, of course, is how to pick the right one among some several thousand candidates of which according to predictions probably only a few can be considered ‘druggable’. On the other hand, there are many well-known drugs or natural products, originating from phenotypic screening, which are efficacious in treating human disorders, yet their targets and mode of action have remained elusive. Finally, lack of knowledge of a compound's protein target profile may not only lead to costly failures in drug development programmes but could also cause severe side effects in patients. Therefore, target deconvolution is a critical process for drug discovery from many perspectives. In the following chapter we will discuss various conceptually different approaches which have been developed in order to identify potential drug targets in settings of human disease. To meet the requirement of comprehensiveness and to avoid any systematic bias, the methods presented include both genomic as well as proteomic strategies ranging from yeast haplo-insufficiency profiling (HIP) to chemical proteomics using human tissues.