Histone deacetylase class I and II isozymes (HDAC class I/II)

Histone deacetylases (HDACs) are a group of enzymes that catalyze the removal of acetyl groups from lysine residues on histone tails and various non-histone proteins (UniProt, 2024). Class I (HDAC1, 2, 3, and 8) and Class II (HDAC4, 5, 6, 7, 9, and 10) isozymes are the primary targets of several FDA-approved drugs, playing a pivotal role in the epigenetic regulation of gene expression (NCBI, 2023). By removing these acetyl groups, HDACs promote a condensed, transcriptionally inactive chromatin state known as heterochromatin (PubMed, 2022). In many cancers, these enzymes are overexpressed or recruited to tumor suppressor promoters, leading to aberrant gene silencing and uncontrolled cell proliferation (StatPearls, 2023). Pharmacological inhibition of these isozymes leads to the accumulation of acetylated histones, which relaxes chromatin structure and allows for the re-expression of genes involved in cell cycle arrest, differentiation, and apoptosis (Nature Reviews Drug Discovery, 2020). HDAC inhibitors, such as vorinostat and panobinostat, typically bind to the zinc-containing catalytic site of these enzymes to block their activity (PubChem, 2024). Beyond oncology, Class I and II HDACs are involved in the regulation of inflammatory cytokines and the survival of neurons, making them targets for autoimmune and neurodegenerative research (PubMed, 2021). Therapeutic challenges include managing systemic toxicities like thrombocytopenia and cardiac arrhythmias, which often arise from the broad activity of non-selective inhibitors (FDA, 2023).

Other names

HDACsHistone deacetylasesLysine deacetylasesKDACs

Inhibition of the enzymatic activity of Class I and II histone deacetylases, resulting in increased acetylation of histone and non-histone proteins, which promotes transcriptional activation of tumor suppressor genes and modulates various cellular pathways (StatPearls, 2023).