Induced proteolysis of pathogenic proteins via degrader molecules, such as Proteolysis Targeting Chimeras (PROTACs), is emerging as a promising therapeutic strategy. In particular, induced proximity of Cullin-RING ubiquitin Ligases (CRLs) with various neo-substrates has proven successful in mediating proteasomal degradation of previously undruggable proteins. Hijacking enzymes to carry out biochemical reactions on neo-substrates stands in stark contrast to conventional pharmacological approaches and exposes degrader molecules to unusually complex pharmacodynamics. While the first PROTACs entered the...