VHL and cancer: To increase potency and target selectivity, small molecules with high affinity and specificity, such as phthalimides recruiting the E3 ligase cereblon (CRBN) [9–14] or VHL-1 recognizing the E3 ligase Von Hippel-Lindau (VHL) [15–17], were introduced into PROTACs to downregulate numerous cancer targets, such as Ikaros family zinc finger protein 1/3 (IKZF1/3) and estrogen-related receptor alpha (ERRα).