Arvinas is developing a new class of drugs that engage the body’s own natural protein disposal system to treat cancers and other difficult-to-treat diseases. As a potential improvement over traditional small molecule inhibitors, PROTACs (Proteolysis-Targeting Chimeras) are able to degrade disease-causing proteins through the cell’s Ubiquitin/Proteasome System, which routinely removes damaged proteins. PROTACTM degraders work by recruiting an E3 ligase to tag the target protein for ubiquitination and degradation through the proteasome, a large complex that degrades the ubiquitinated protein into small peptides. After destruction of the protein, the PROTAC is released to continue its seek and destroy mission.
Inhibition vs. Degradation
By removing target proteins directly rather than merely blocking them, PROTACs can provide multiple advantages over small molecule inhibitors, which can require high systemic exposure to achieve sufficient inhibition, often resulting in toxic side effects and eventual drug resistance. In addition, no inhibitors have been identified for a majority of the targets of interest in drug development. By contrast, our PROTAC technology has been shown to be robust, demonstrating high potency and durability in the preclinical setting, and degrading more than 85% of proteins tested across multiple target classes and therapeutic areas. Our broad platform is focused on high value targets—initially in cancers—and we believe it has the potential to dramatically expand drug development in the most difficult-to-treat diseases.