Drug Discovery
PROTAC Drug Discovery
PROTACs, or PROteolysis-TArgeting Chimeras, are an innovative class of small molecules designed to eliminate disease-causing proteins inside cells. Unlike traditional drugs that simply block a protein’s activity, PROTACs work by triggering the complete degradation of the target protein. This is achieved by hijacking the cell’s natural waste-disposal system—the ubiquitin-proteasome pathway.
Each PROTAC molecule has two functional ends connected by a linker:
- One end binds to the target protein.
- The other binds to an E3 ubiquitin ligase, an enzyme that tags proteins for destruction.
By bringing these two components together, PROTACs form a “ternary complex” that marks the target protein for degradation by the proteasome. Importantly, PROTACs act catalytically, meaning a single molecule can degrade multiple copies of the target protein.
This approach offers several advantages:
- Expands druggable targets, including proteins previously considered “undruggable.”
- Overcomes drug resistance, since the protein is removed entirely rather than just inhibited.
- Potentially lower doses, reducing side effects.
PROTAC technology is being explored for cancer, neurodegenerative diseases, immune disorders, and even viral infections, making it a powerful tool for next-generation precision medicine
Molecular Glues
Molecular glues are a cutting-edge class of small molecules that work by modulating protein–protein interactions inside cells. Unlike traditional drugs that block or activate a single protein, molecular glues act as a “bridge,” bringing two proteins together or stabilizing their interaction. This unique mechanism can trigger targeted protein degradation or alter protein function, opening new possibilities for treating diseases.
One of their most exciting applications is in targeting proteins previously considered “undruggable”, such as those involved in cancer, neurodegenerative disorders, and immune-related diseases. By leveraging the cell’s natural degradation machinery, molecular glues can selectively eliminate harmful proteins, offering a powerful approach for precision medicine.
Compared to other technologies like PROTACs, molecular glues are smaller, simpler, and often more drug-like, making them attractive candidates for next-generation therapeutics. As research advances, these molecules are poised to revolutionize drug discovery and expand treatment options for challenging diseases.