p53 Y220C Degradation as an Anti-Cancer Strategy

Most medicines work by “throwing a spanner in the works” of their target biological protein, preventing them from causing a disease. This approach has served humanity well, and contributed to rising life expectancies over many decades. A key limitation to this classical approach is that a drug molecule must have a 1:1 interaction with its protein target in order for the “spanner” to work. An emerging strategy in medicinal chemistry seeks to overcome the 1:1 drug:protein requirement by targeted protein degradation. In this model, a drug compound doesn’t stop the protein from working, it signals for the degradation of that protein. Because the drug molecule survives, a single molecule can “take out” many copies of a protein. The protein degradation strategy is new enough that it hasn’t been fully explored. This project is about studying protein degradation in the context of p53, the most commonly mutated protein in all of cancer. Our multidisciplinary team is very excited to build on our existing preliminary results to address this challenge.