The SLAS Meeting in Boston presented the opprtunity to meet as new established SIG and to discuss questions in the TPD field. Thanks to our speakers Marina Nelen (Foghorn) and Christroper Roberts who presented their views on Proximity assays.
The podium discussion delved into the evolving landscape of targeted protein degradation (TPD) drug discovery, emphasizing the pivotal role of well-established biochemical, biophysical, and cell-based assay technologies. These platforms serve as crucial tools for screening and testing proximity-inducing modalities within and beyond the realm of TPD. A focal point of debate revolved around the optimal starting point for the discovery of molecular glue (MG). Participants deliberated whether to initiate the process with biochemical and biophysical assays for proximity inducer identification, followed by cell-based assays to assess degradation, or vice versa. The consensus reached was that the approach hinges on various factors. The discussion underscored that when armed with a specific E3:target pair and structural insights, a more rational design strategy coupled with protein-protein interaction (PPI) assays may be preferred. Conversely, in scenarios where target binders are available and E3 ubiquitin ligase agnosticism persists, commencing with a phenotypic screen could be advantageous. Ultimately, the decision rests on the repertoire of tools at hand and the specific scientific queries necessitating answers.
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Markus Queisser
Scientific Director
GlaxoSmithKline
Stevenage
441438764034
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