PROTACs, unraveling the Ubiquitin Code

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PROTACs, or PROteolysis Targeting Chimeras, are representative of a new class of small molecules of bifunctional design to target and degrade specific proteins that were once considered “undruggable.” PROTACs harness the ubiquitin proteasome system (UPS) to degrade these proteins.

By design, PROTACs are bifunctional molecules that bind to the target protein of interest and an E3 ubiquitin ligase simultaneously. This binding allows for ubiquitin to be transferred from the E3 ligase onto the target protein of interest, marking it for degradation via the proteasome. By inducing targeted protein degradation, PROTACs can degrade specific disease-causing proteins, offering a novel strategy for treating a wide variety of diseases like cancer, neurodegenerative disorders, and autoimmune diseases. 

The promising reign of PROTACs in preclinical and clinical studies gives hope to a new avenue of successful therapeutics. With their unique design and mechanism, PROTACs are leading the way as a new approach to innovative drug discovery and development.