Most medicines today work by blocking the activity of disease-causing proteins. One major limitation of these drugs is—the harmful protein remains inside the cell and can often regain its function once the drug is removed. PROTACs (PROteolysis TArgeting Chimeras)are bifunctional small molecules designed to harness the body’s natural protein disposal system. Rather than blocking a protein’s active site, they recruit the cell’s own machinery to destroy the target protein.
What is PROTAC molecule and how it works?
A PROTAC molecule consists of three components:
- A ligand that binds the disease-causing protein.
- A ligand that binds an E3 ubiquitin ligase, an enzyme involved in protein degradation.
- A chemical linker connecting the two ligands.
Once both proteins are brought together, the E3 ligase labels the target protein with ubiquitin, signaling it for destruction by the proteasome, the cell’s protein recycling complex.
Advantages Over Conventional Drugs
| Conventional Inhibitors | PROTACs |
|---|---|
| Block protein activity | Destroy the protein |
| Continuous drug exposure required | Prolonged effect after degradation |
| Limited to druggable proteins | May target previously undruggable proteins |
| Resistance develops through mutations | Potential to overcome some resistance mechanisms |
| One drug binds one protein | One PROTAC can degrade multiple proteins sequentially |
Conclusion: By harnessing the cell’s natural protein degradation machinery, these innovative molecules shift the therapeutic strategy from blocking disease-causing proteins to eliminating them entirely. PROTACs have the potential to transform the treatment of cancer, neurodegenerative disorders, autoimmune diseases, and other conditions that have been challenging to manage till today.
How do you see the future of this new medicines?