There have been a number of PROTACs reported that degrade HDAC3 with selectivity over other HDAC isoforms.56,58,60,61 Using a hydrazide pan HDAC1-3 inhibitor, an uncommon HDAC ligand, Xiao et al. were able to synthesise and identify a HDAC3 selective degrader, 7, incorporating an alkyl linker and a VHL ligand in the PROTAC (Chart 2).60 PROTAC 7 exhibited an impressive DC50 value of 42 nM in breast cancer MDA-MB-468 cells with no significant changes in HDAC1, HDAC2 or HDAC6 abundance. The gene discussed is HDAC9; the disease is breast cancer.