Histone Deacetylases as Targets for Multiple Diseases

Abstract

Inhibition of Histone deacetylases (HDACs) has been emerged as important approach to reverse aberrant epigenetic changes associated with various cancerous and non-cancerous diseases. The field of histone deacetylase inhibitors (HDIs) is moving into a new phase of development. The structure of histone deacetylases is well-established and the active sites have been well identified. Various drugs targeting this enzyme are in the pipeline for the treatment of different diseases. Since first-generation HDAC inhibitors proved their clinical fruitfulness and also second generation inhibitors are rationally designed with improved specificity, experts believe that this class will emerge in the treatment of various diseases. Considering these facts present review focuses on HDACs and developments of HDIs in the treatment of various diseases.

Biological approaches for hypertrophic scars

“…Reducing the main derived fibroblast is an important way. Inhibitors of histone deacetylase have been reported play roles in regulation of fibrotic gene expression . Suppressing histone deacetylase limits the proliferation of lung fibroblasts and inhibits fibrosis‐related gene transcription, leading to the anti‐fibrotic ending .…”

“…Inhibitors of histone deacetylase have been reported play roles in regulation of fibrotic gene expression. 111 Suppressing histone deacetylase limits the proliferation of lung fibroblasts and inhibits fibrosis-related gene transcription, leading to the anti-fibrotic ending. 112 Trichostatin A, as the potent molecule, it could inhibit the proliferation of fibroblasts in vivo or in vitro.…”

Targeting Selective Autophagy of Insoluble Protein Aggregates

“…The main indication for HDAC inhibitors is cancer [73,74] but other clinical indications are supported by preclinical evidence [75]. Vorinostat/Zolinza ® [76] and romidepsin/Istodax ® [77] (respectively the hydroxamate SAHA-5.19 and the cyclic depsipeptide FK228-5.20, Figure 5.5) are broad spectrum HDAC inhibitors, acting on all HDAC isoforms.…”

Overexpression of <em>HDAC9</em> is associated with poor prognosis and tumor progression of breast cancer in Chinese females

“…Data in several previous studies reveal that an aberrant expression of HDACs has been detected in many tumor samples. 10 , 11 In addition, HDACs have been found to inhibit tumor suppressor expression by binding to the promoter region. 12 , 13 HDAC9 , a subtype of HDAC , has been investigated in some types of human cancers.…”