Developments in modulating protein function for effective target validation

The targets of more than 95% of clinically approved drugs are proteins. Thus, the plethora of targets derived from genomics and proteomics efforts must be validated at the protein level. However, most of the preferred target validation technologies are gene- or transcript-based. Protein-based or proteinetic approaches, which are more relevant to determine target druggability, are now emerging. Luis Menandez-Arias, Pierre Chatelain, Bernard Masereel Technologies focusing on the direct modulation of protein activity, such as chromophore-assisted laser inactivation, provide a complementary approach to gene knockout and other validation techniques targeting gene expression. Protein inactivation techniques show high spatial and temporal resolution and can be used to validate novel targets (i.e. a single domain of a protein), missed by other inactivation strategies. This review was selected because protein inactivation technologies are expected to play a key role in the development of functional proteomics, through the identification of multiple interactions between gene products, and addressing the role of proteins in complex cellular pathways.