A Box of Enzymes for Multiple Diseases: Discovering the Truly Role of Selective HDAC Inhibitors

Dear Colleagues,

A fine tuning of the epigenetic processes regulates gene transcription and genomic stability and maintains normal cell growth, development, and differentiation. Histone deacetylases (HDACs), also termed epigenetic erasers, are responsible for deacetylating the lysine residues on the tails of histones, thereby modifying chromatin structure and gene expression. There are non-histone proteins and several cytoplasmic proteins that are regulated by HDACs, as well. Various HDAC inhibitors (HDACis), endowed or not with isoform selectivity, have been developed for over three decades. To date, however, only five HDACis have been approved for cancer therapy. Nevertheless, HDACis hold promising potential therapeutic utility for other diseases, including neurological disorders and retinal and cardiovascular diseases. In the frame of selective inhibition of one of the 18 the HDAC isoforms (11 with a zinc-dependent enzymes and 7 sirtuins), a promising and challenging task is the discovery of proteolysis-targeting chimeras (PROTACs). HDAC based-PROTACS are heterobifunctional molecules that couple an HDAC ligand with a ligand for an E3 ligase such that the HDAC enzyme becomes polyubiquitinated and degraded by the proteasome. This emerging field of research could provide a new and innovative approach and deliver a proof of concept for the selective inhibition of a specific HDAC isoform in a certain diseases.

In this frame, we would like to invite original articles and reviews focusing on the understanding of the role of HDACi and the HDAC enzyme in various disease states, also including medicinal chemistry efforts around the design of new candidate inhibitors. In addition, articles associated with model disease systems, drug resistance, and therapy, with an eye on the most modern approaches, would be of high value for this Special Issue.

Dr. Stefania Butini
Guest Editor

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