I Technical Principle of PROTAC
Five elements 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, PROTAC™ (Proteolysis-Targeting Chimera) protein degraders are able to degrade disease-causing proteins through the cell’s Ubiquitin/Proteasome System, which routinely degrades proteins. PROTAC™ protein 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 the protein is degraded, the drug is released to continue its degradation mission.
II The Advantages of PROTAC
When the first human genome was sequenced, researchers finally got a glimpse of the true dimensions of our proteome—the tens of thousands of proteins responsible for sickness and health. Ever since, scientists have explored the morass for drivers of diseases, generating a long wish list of proteins they’d like to control.
But even as they add to the list, drug hunters live with a maddening reality: So many of its entries are out of reach. Conventional small-molecule and antibody drugs can access only about 20% of the proteins we make. So when a new technology comes along promising to tap into the other roughly 80%, everyone pays attention. And PROTAC is the attention.
INHIBITION VS. DEGRADATION
By removing target proteins directly rather than merely blocking them, our PROTAC™ protein degraders may provide multiple advantages over small molecule inhibitors.
1. Cellular Potency and Catalytic Effect
Most small molecule-induced pharmacology is driven by the requirement for maintenance of high equilibrium target occupancy