Furthermore, proteomic analysis confirmed selective reduction of HDAC6 levels as well as collateral degradation of MIER1 by 17c. A possible mechanism for degradation of MIER1, could be that 17c forms a ternary complex with the HDAC1/2-MIER1 complex and the CRL4 CRBN E3 ligase, leading to the specific (poly)ubiquitination of MIER1 but not of HDAC1/2 and thus to MIER1 degradation. This mechanism was also discussed by Xiong, Donovan et al. in their chemo-proteomics exploration of HDAC degradability. To conclude, our findings provide valuable insights into the development of new selective HDAC6 degraders based on an alternative ZBG, which hold promise for therapeutic application in HDAC6 related diseases. Furthermore, our compounds resemble the first reported hydrazide-based selective HDAC6-targeting PROTACs.