The future of drug discovery: E3scanTM and beyond
by Ksenya Cohen Katsenelson, Ph.D., Senior Scientist Group Leader, Eurofins Discovery, ksenyacohen@eurofinsus.com
In the past two decades, a new paradigm-shifting approach to drug discovery has emerged. Targeted Protein Degradation (TPD) offers a different approach for drugging a disease target. Instead of inhibiting an interaction interface or catalytic activity, the molecular target is degraded. TPD uses small molecules to hijack the body’s cellular degradation machinery by recruiting E3 ubiquitin ligases to proteins of interest, thereby inducing ubiquitin dependent degradation of molecular targets. The potential of this novel approach is boundless, as it opens the door for the development of new chemical entities for proteins previously thought to be undruggable, including transcription factors, scaffolds, and other non-enzymatic proteins, which constitute 80% of the human proteome.
As a leader in drug discovery services, Eurofins Discovery launched its novel TPD service, E3scan™, in the middle of the COVID-19 pandemic. E3scan is based on previously established KINOMEscan® technology, which utilises a substrate-recruitment, site-directed competition binding assay. The platform now includes assays against 12 different E3 ligases, as well as individual substrate recognition domains for substrate selectivity determination. This platform is being constantly refined and expanded with additional assays ready for launch in late 2021 and in 2022.
But what lies beyond the E3scan and the KINOMEscan technology platforms? With this novel TPD space now rapidly evolving, almost every pharmaceutical company has a division in this space. Several pharmaceutical startup companies that were launched in the past few years are solely dedicated to the TPD space. Therefore, with so many different companies looking for degrader drugs for multiple new targets, the possibilities are endless for this area of drug discovery. The future of finding new drugs for targets that were previously considered to be undruggable is bright. In light of this, Eurofins Discovery is planning to remain the leader in drug discovery innovation, and will pursue the development of novel technologies and assays to support this exciting new era in drug discovery. These efforts will hopefully lead to the cure of many more human diseases.
For more information, visit: www.eurofinsdiscoveryservices.com/services/in-vitro-assays/protein-degradation/