Biotech Informers

Proteolysis-targeting chimeras (PROTACs) are a novel class of small molecules that have the ability to induce the targeted degradation of specific proteins within cells. This technology represents a promising approach for developing therapeutic interventions for various diseases, including cancer, inflammatory disorders, and genetic diseases.

PROTACs consist of three key components: a ligand that selectively binds to the target protein, a ligand that binds to an E3 ubiquitin ligase, and a linker that connects the two ligands. The E3 ubiquitin ligase recognizes the target protein and tags it with ubiquitin molecules, which serve as a signal for the cell’s degradation machinery to break down the protein.

The key advantage of PROTACs over traditional small molecule inhibitors is that they can target proteins that are considered “undruggable” by conventional methods. This is because PROTACs do not directly inhibit the target protein’s function, but instead induce its degradation, thereby eliminating the protein from the cell.

PROTACs can also be designed to selectively degrade specific isoforms or mutants of a protein, while leaving other isoforms or the wild-type protein intact. This provides a level of specificity that is not achievable with traditional small molecule inhibitors.

The development of PROTACs has been facilitated by advances in chemical synthesis, protein engineering, and structural biology. Several PROTACs have been developed that target proteins involved in cancer, such as BRD4 and BCL-xL, and have shown promising results in preclinical studies.

While the development of PROTACs is still in its early stages, the potential of this technology is vast. The ability to selectively degrade disease-causing proteins could revolutionize the treatment of a wide range of diseases and improve the lives of countless patients.