Technologies and trends

PROTACs® - A promising approach to expand drug discovery

PROTACs® have the potential to target previously "undruggable" proteins. This opens up completely new possibilities in the development of new drugs and therapeutic modalities.

What are PROTACs®?

PROTAC® stands for proteolysis targeting chimera. This is a molecule that is capable of removing specific unwanted proteins by breaking proteins down into smaller amino acids. PROTACs® consist of two covalently linked protein-binding molecules: one capable of engaging an E3 ubiquitin ligase, and another that binds to a target protein meant for degradation.

PROTACs® only need to bind to their targets with high selectivity rather than preventing the target protein's enzymatic activity. This means that it’s possible to retool previously ineffective inhibitor molecules as PROTACs® for next-generation drugs.

What is the potential of PROTAC® for pharmaceutical research?

Today, up to 80 percent of the human proteome is still considered as undruggable by small molecules. PROTACs® might be able to address an array if novel disease-relevant targets.

PROTAC® protein degraders have the potential to be an improvement over traditional small molecule inhibitors because they are able to degrade disease-causing proteins. After the protein is degraded, the drug is released to continue its degradation mission.

By removing target proteins directly rather than blocking them, protein degraders could provide multiple advantages over small molecule inhibitors. In order to sufficiently inhibit the protein, small molecule inhibitors can require high systemic exposure which often results in toxic side effects and eventual drug resistance. In addition, for a majority of the targets of interest in drug development, no inhibitors have been identified.

The PROTAC® technology platform, on the other hand, has been shown to be robust, demonstrating high potency and durability in the preclinical setting, as well as degrading more than 90% of proteins tested across multiple target classes and therapeutic areas. It is focused on high-value targets—initially in cancers—and we believe it has the potential to dramatically expand drug development in many difficult-to-treat diseases.