Most drugs are designed to block one specific function of a disease-causing protein. But over 80% of human proteins are not accessible via this approach and are generally considered “undruggable”.

Although many important drivers of disease have been known for decades, they are simply out of reach. Glue degraders circumvent this limitation as they do not rely on the requirements of traditional pharmacology. The right glue degrader can attack any given target protein in the cell and lead to its removal.

The most versatile modality

Glue degraders are small molecules that bring a target protein into proximity of a ligase protein, leading to the degradation of the target protein via the natural protein recycling machinery present in every cell.

Compared to other types of drugs, glue degraders have vast advantages: they can target any protein in the cell, they are exceptionally selective against a given target protein, and their effect is catalytic, meaning once a protein is degraded, they move on to the next protein and repeat the cycle.

Target
protein
Proteasome
Degraded
target protein
Glue

WE ARE PIONEERS

As exciting as glue degraders are, they are very difficult to find. Before Proxygen was founded, there was no systematic way of identifying glue degraders. We have built and are constantly developing a highly versatile glue degrader identification platform, deploying the right tools and technologies for a given target, enabling us to quickly find glue degraders against proteins of high medical relevance.

Features

Glue degraders circumvent many limitations of traditional pharmacology, thereby expanding the druggable proteome to almost 100%

Their prime selectivity allows for targeting specific members of highly conserved protein families

Instead of just blocking, glue degraders eliminate harmful proteins which often leads to prolonged effects

Once a glue degrader has marked its target for degradation, the same molecule moves on to the next protein to repeat the cycle, leading to far lower doses required for the same effect

“These are trailblazing times for the pharmacology of glues, with the Proxygen team leading at the new frontier of scientific discovery. It feels like a thrilling horseback gallop, the wind in your hair as you explore new territories and vistas at exhilarating speed.”

Giulio Superti-Furga