Higher throughput techniques for PROTAC drug discovery

PROteolysis-TArgeting Chimeras (PROTACs) are an exciting development in drug discovery with the potential for modulation of targets once considered ‘undruggable’.

A PROTAC is designed with two ‘warheads’, one binding to the protein target of interest (TOI) and the second binding to an E3 ligase (typically VHL or CRBN). The two warheads are joined by a flexible linker that allows the E3 ligase to ubiquitinate the TOI - targeting it for degradation by the intracellular ubiquitin proteasome system.

However, a bottleneck exists in the relatively slow throughput of the methods that have traditionally been used to discover and assess the performance of new PROTAC molecules. We therefore demonstrate here several techniques, including biophysical and automated western blotting, we at Aurelia Bioscience employ to increase the throughput of PROTAC drug discovery.