Targeted Protein Degradation (TPD) is a revolutionary therapeutic strategy leveraging the cell's natural waste disposal system to selectively remove...
TPD is a therapeutic strategy that uses small molecules to redirect the cell's natural protein degradation machinery (the ubiquitin-proteasome system) to selectively destroy specific disease-causing proteins.
Traditional inhibitors block protein function, while TPD completely removes the protein from the cell. This can lead to more sustained therapeutic effects and the ability to target proteins previously considered 'undruggable'.
PROTACs (PROteolysis TArgeting Chimeras) are a key class of TPD agents. They are bifunctional molecules that simultaneously bind to a target protein and an E3 ubiquitin ligase, inducing the target's ubiquitination and subsequent degradation.
TPD holds promise for treating a wide range of diseases, including various cancers, neurodegenerative disorders like Alzheimer's and Parkinson's, autoimmune conditions, and viral infections, by eliminating critical pathogenic proteins.
Key advantages include complete protein elimination, a catalytic mechanism that may require lower drug doses, the ability to target proteins lacking active sites ('undruggable' proteins), and potential for overcoming drug resistance mechanisms.