Plasticity in designing PROTACs for selective and potent degradation of HDAC6

Abstract

HDAC6 (histone deacetylase 6) catalyses the deacetylation of non-histone substrates, and plays important roles in cell migration, protein degradation and other cellular processes. Here we report that CRBN-recruiting PROTAC NH2, which introduces pomalidomide at the benzene ring of Nex A, reaches comparable degradation efficiency of HDAC6 compared to aliphatic-chain-introducing PROTAC NP8.