Degraders were on the front page of the Friday edition of the WSJ Business and here's a little context for people like my dad who are not bio focused. Drugs that target proteins usually work by binding the protein of interest and preventing it from working properly. But, degraders work by connecting the protein of interest to a junk processor called E3UL. The degrader brings the junk processor to the disease-causing protein and essentially makes it way more likely that the disease-causing protein is going to get tagged by the junk processor for destruction. And actually, thalidomide was the first degrader, except we didn't know it at the time. It was offered as a morning sickness antidote in the late 1950s but was later recalled after it caused birth defects. Decades later in the 1990s, it came to be used in multiple myeloma after clinical trials showed it worked well. It was a backbone of treatment. Its derivatives are still the cornerstone of myeloma treatment regimens. Despite its use in the clinic, we didn't really know how it worked and that it was a degrader until 2010. Knowing how a drug works biochemically doesn't always come before figuring out if a drug works for patients. Back to degraders. Degraders attack proteins that live INSIDE cells. Proteins that cause disease that exist inside cells are infinitely tougher to target than proteins that live on the OUTSIDE of cells. For example, antibodies can attack proteins that live on the outside of cells and we as humans have gotten quite good at making antibodies. The cell is a place packed full of billions of molecules buzzing around participating in billions of reactions. Degraders bring two things into proximity to force a specific single process to occur amidst the chaos. Degraders are a specific instance of a general class of drugs called molecular glues that act to bring a disease-causing protein into close proximity with something else in order to treat disease. Daraxonrasib, the pancreatic cancer drug that has doubled overall survival, is a molecular glue that brings together KRASG12X (disease-causing protein) and CYPA so that CYPA blocks access to KRASG12X.