Susanne Müller-Knapp, SGC Oxford, UK
The SGC (Structural Genomics Consortium) is an academic organisation with laboratories at the universities of Oxford (UK), Toronto (Canada), North Carolina US) Campinas (Brazil) and Frankfurt (Germany). The consortium encompasses a large public-private partnership involving currently nine pharmaceutical companies.
One of the main topics of the SGC is to generate chemical probes, well-characterized, potent, selective and cell-active tool compounds, for kinases and epigenetic proteins. These molecules are essential tools in target validation to understand the biology of their cognate proteins and are made available to the scientific community. In order to draw conclusions regarding the biological activity of newly developed inhibitors it must first be confirmed that their observed cellular effect is due to the inhibition of the respective enzyme rather than uncharacterized off-target activity or nonspecific effects. In addition to extensive in vitro profiling, thorough cellular characterisation is necessary. Examples of assessing cellular target engagement of kinase inhibitors and cellular selectivity are presented.