The Process and Strategy for Developing Selective Histone Deacetylase 3 Inhibitors

Abstract

Histone deacetylases (HDACs) are epigenetic drug targets that have gained major scientific attention. Inhibition of these important regulatory enzymes is used to treat cancer, and has the potential to treat a host of other diseases. However, currently marketed HDAC inhibitors lack selectivity for the various HDAC isoenzymes. Several studies have shown that HDAC3, in particular, plays an important role in inflammation and degenerative neurological diseases, but the development of selective HDAC3 inhibitors has been challenging. This review provides an up-to-date overview of selective HDAC3 inhibitors, and aims to support the development of novel HDAC3 inhibitors in the future.

Design, synthesis and docking study of acyl thiourea derivatives as possible histone deacetylase inhibitors with a novel zinc binding group

“…inhibition of growth was observed at the highest concentration used for both compounds (figure 8). This can possibly be considered, in agreement with previous reports [3,4], that the synthesized compounds might exhibit relative specificity in inhibiting HDACs that are overexpressed in cancer cells. Besides, HDAC1 and HDAC2 are absent in normal breast cells [36,37] which further supports this low cytotoxicity in normal tissue, Furthermore, it was hypothesized that normal cells, in contrast to cancer cells, could struggle the inhibitory action of HDAC inhibitors and compensate for the inhibited vital pathways since they have multiple, alternative epigenetic regulatory pathways [38].…”

Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group

“…No more than 12% of inhibition of growth was observed at the highest concentration used for both compounds (Figure 9). This might possibly be considered, in agreement with previous reports [3,4], that the synthesized compounds might exhibit relative specificity in inhibiting HDACs that are overexpressed in cancer cells. Besides, HDAC1 and HDAC2 are absent in normal breast cells [43,44] which further supports this low cytotoxicity in normal tissue.…”

“…The deacetylation process results in the compaction of nucleosomes and subsequently the repression of gene transcription. Many reports demonstrate that HDACs are overexpressed in several types of cancer [3,4]. Therefore, they represent a valuable target for cancer treatment [5].…”

Biosimilar Interchangeability and Emerging Treatment Strategies for Inflammatory Bowel Diseases: A Commentary

“…Combinations of anti-TNF-α biosimilars with anti-adhesion, anti-integrin, and interleukin 12/23 antagonists (more common in children than in adults) as well as Janus kinase inhibitors (tofacitinib, peficitinib, upadacitinib, filgotinib), sphingosine-1-phosphate [S1P] receptor modulators (ozanimod, etrasimod), phosphodiesterase-4 inhibitors (apremilast), selective histone deacetylase 3 inhibitors (givinostat, vorinostat) and/or substitutions of phosphatidylcholine (LT-02) (i.e., agents with different mechanisms of action) are on research agendas in various phases and treatment horizons [49][50][51][52][53][54][55][56]. Brief research reports on the use of small molecules and combinations with either the reference product or the biosimilar for potential treatment are nascent and based only on clinical experience.…”