Dissecting Histone Deacetylase 3 in Multiple Disease Conditions: Selective Inhibition as a Promising Therapeutic Strategy

Abstract

The acetylation of histone and non-histone proteins has been implicated in several disease states. Modulation of such epigenetic modifications has therefore made histone deacetylases (HDACs) important drug targets. HDAC3, among various class I HDACs, has been signified as a potentially validated target in multiple diseases, namely, cancer, neurodegenerative diseases, diabetes, obesity, cardiovascular disorders, autoimmune diseases, inflammatory diseases, parasitic infections, and HIV. However, only a handful of HDAC3-selective inhibitors have been reported in spite of continuous efforts in design and development of HDAC3-selective inhibitors. In this Perspective, the roles of HDAC3 in various diseases as well as numerous potent and HDAC3-selective inhibitors have been discussed in detail. It will surely open up a new vista in the discovery of newer, more effective, and more selective HDAC3 inhibitors.

Carboranes as unique pharmacophores in antitumor medicinal chemistry

“…Histone deacetylases (HDACs) are known to be responsible for the global silencing of tumor-suppressor genes. 243 , 244 , 245 , 246 , 247 , 248 , 249 Overexpression of HDACs was shown to be linked to several cancer types, and their selective inhibition results in potentiated anticancer effects. 249 Treatment with histone deacetylase inhibitors (HDACis) can reverse this process and restore normal cell function.…”

Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives

“… 219 , 220 Histone deacetylase inhibitors (HDACi) serve as transcriptional activators, and they have been proven to be beneficial in many pathological conditions, as reported in several recent reviews. 221 − 223 Mammalian genome encodes 11 HDACs categorized into four different classes, but the precise role of each isoform in cellular function is not yet completely understood. 224 HDACi have represented useful tools to help clarify these issues, as they inhibit different HDACs mostly by interacting with their catalytic sites, leading to decreased deacetylation of histones and proteins.…”

Histone Deacetylase 3: A Potential Therapeutic Target for Atherosclerosis

“…They modulate SMRT activity in NCoR complex during HDAC3 activation [ 20 , 21 ]. The highly conserved SANT2 region is an important component of the histone interaction domain and is required for the binding and activation of HDAC3 [ 22 , 23 ].…”