Figure 2.

Schematic of RAS degrader mechanism of action

(1) Linker-based degraders and PROTACs fuse a protein binding domain or chemical compound to a ligand for an E3 ligase. The degrader creates a ternary complex between the protein of interest, such as RAS, and the E3 ubiquitin machinery.¹⁰ E2 transfers ubiquitin to the protein of interest which allows it to be degraded by the 26S proteasome.¹⁰⁷ (2) Direct proteolysis occurs where the protease binds to and cleaves the protein of interest, for example, RAS, and the protein is subsequently degraded. Figure created with Biorender.com.