PROTAC^® (PROteolysis TArgeting Chimeras) Degraders are bifunctional small molecules that harness the Ubiquitin Proteasome System (UPS) to selectively degrade target proteins within cells. They represent an exciting new modality, repurposing small molecule chemical tools to achieve selective degradation (knock-down) of target proteins. Moreover, they have the potential to expand the ‘druggable proteome’, since they can be used to degrade proteins that although bound, are not effectively inhibited, by small molecules. As research tools they offer an attractive alternative to genetic methods for inducing target protein knock-down/knock-out.

We present a comprehensive workflow solution for Degrader development programs. Starting with target validation principles and the TAG technology platform for exploring degradation of your target, we will then present modular chemical building blocks (PROTAC^® Panel Builder / Degrader Building Blocks) and physicochemical design principles (1) to feed into medicinal chemistry pipelines. Finally, we will discuss effective solutions and assays for profiling candidate Degraders. We present both cell-free (in-vitro ubiquitination) and cell-based (Simple Western^™) assays with recent data from an automated assay for profiling neosubstrate recruitment by Cereblon-harnessing Degraders. PROTAC^® is a registered trademark of Arvinas Operations, Inc., and is used under license.

		Hannah Maple, Ph.D. Innovation Manager for Tocris Bio-Techne
Hannah Maple, Ph.D. is the Innovation Manager for Tocris, a Bio-Techne brand. In this role she leads a team responsible for identifying, developing and commercializing innovative new tools and technologies for Life Sciences research. Prior to joining Tocris, Hannah was the manager of the MRC-funded Metabolomics NMR Facility at Bristol University. She has also worked for the pharmaceutical company, UCB, where she was a Senior Scientist developing and implementing new biophysical techniques for studying protein structure, interactions and function. Hannah received her PhD in Chemistry from the University of Bristol.