Mechanism of Action for HDAC Inhibitors-Insights from Omics Approaches

• Published in: International journal of molecular sciences Vol. 20; no. 7; p. 1616
• Main Authors: Li, Wenbo, Sun, Zheng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2019; MDPI
• Subjects: Acetylation; Acute lymphoblastic leukemia; Adenocarcinoma; Binding sites; Breast cancer; cancer treatment; chemoproteomics; Chromatin; Colon; Deoxyribonuclease; Deoxyribonucleic acid; Digestive enzymes; DNA; DNA methylation; DNA sequencing; Enzymes; epigenomics; Gene expression; Genomes; HDAC2 protein; Hepatocellular carcinoma; Histone deacetylase; histone deacetylase inhibitors (HDIs); Histone H3; Histones; Kinases; Leukemia; Lymphatic leukemia; Lymphocytes B; Lymphoma; metabolomics; Nuclease; Nucleosomes; Proteins; proteomics; Regulatory sequences; Review; Studies; Transcription termination; transcriptomics; Transposase; cancer treatment; chemoproteomics; histone deacetylase inhibitors (HDIs); proteomics; metabolomics; transcriptomics; epigenomics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20071616

Histone deacetylase inhibitors (HDIs) are a class of prominent epigenetic drugs that are currently being tested in hundreds of clinical trials against a variety of diseases. A few compounds have already been approved for treating lymphoma or myeloma. HDIs bind to the zinc-containing catalytic domain of the histone deacetylase (HDACs) and they repress the deacetylase enzymatic activity. The broad therapeutic effect of HDIs with seemingly low toxicity is somewhat puzzling when considering that most HDIs lack strict specificity toward any individual HDAC and, even if they do, each individual HDAC has diverse functions under different physiology scenarios. Here, we review recent mechanistic studies using omics approaches, including epigenomics, transcriptomics, proteomics, metabolomics, and chemoproteomics, methods. These omics studies provide non-biased insights into the mechanism of action for HDIs.