HDACs are crucial targets for cancer treatment, butdeveloping drugsspecifically targeting individual HDAC isozymes is difficult due tothe preserved catalytic domain.122 As statedby Smalley et al, Von Hippel-Lindau (VHL), E3-ligase PROTACs wereoptimized to target HDAC1 and HDAC3 in colorectal carcinoma cells(HCT116).123 By modifying the linker lengthand VHL ligand, PROTAC molecules 7, 9, and 22 were identified, effectivelytargeting and degrading HDAC1 or HDAC3 with micromolar DC50 values. The gene discussed is VHL; the disease is colorectal carcinoma.