PROTACs: Revolution on the horizon in the fight against many diseases

The research has taken nearly 30 years. PROTACs (proteolysis-targeting chimeras) are finally entering the drug market. Unlike traditional treatments that block the activity of disease-causing proteins, these molecules permanently destroy them.

While conventional drugs are like defenders trying to stop an attacker on a soccer field, PROTACs act more like a referee. They can send the player—that is, the protein responsible for the disease—off the field.

In fact, PROTACs take advantage of the cells’ natural recycling system. They bind simultaneously to the target protein (which causes the disease) and to a marker enzyme, which can “tag” the unwanted protein so that it is destroyed by the proteasome, a molecular shredder. This mechanism makes it possible to target thousands of proteins previously considered inaccessible to conventional treatments, as a single PROTAC molecule can repeat the process dozens of times.

Developed in 1998 by Craig Crews and Raymond Deshaies, this approach has been realized with vepdegestrant, a treatment for resistant breast cancer. Currently being evaluated for other types of cancer as well as neurodegenerative, autoimmune, and inflammatory diseases, PROTACs could become, according to New Scientist, one of the major therapeutic advances of recent decades.