Small molecules – like aspirin, some antibiotics and many cancer treatments – make up around 90% of approved pharmaceutical drugs. Often, they bind at the active site of a target protein to prevent it from carrying out its known biological function. 

But not all proteins can be targeted in this way: around 80% of disease-related proteins can’t be bound by traditional small molecule drugs.  

This is often because they lack a well-defined binding site, or because the binding site is difficult to access.  

Targeted protein degradation (TPD) takes a different approach. Rather than binding to inhibit the target protein, TPD helps connect the target with a ubiquitin tag.  

This marks the target for destruction by triggering the ubiquitin proteasome system – each cell’s natural waste disposal system – to break the target protein down. 

Because TPD can work isn’t constrained to active sites, it offers great promise for targets that have previously been “undruggable” – potentially leading to new, much-needed therapies for complex conditions like cancer, infectious diseases and neurodegeneration.