Class I Histone Deacetylases and Class IIb Histone Deacetylase 10 (Class I HDACs and HDAC10)

Class I Histone Deacetylases (HDAC1, 2, 3, and 8) and Class IIb Histone Deacetylase 10 (HDAC10) are essential enzymes that regulate gene expression and cellular survival through the removal of acetyl groups from lysine residues and polyamines [4, 18]. Class I HDACs are predominantly located in the nucleus, where they modulate chromatin structure and repress the transcription of various genes, including those involved in cell cycle control and apoptosis [12, 19]. HDAC10 is distinct within the Class IIb family, primarily functioning as a polyamine deacetylase that supports late-stage autophagy and protects cells from metabolic stress [2, 11]. Overexpression of these enzymes is frequently observed in many cancers, contributing to the silencing of tumor suppressor genes and the promotion of malignant phenotypes [1, 23]. Drugs targeting this specific combination of HDACs, such as chidamide (tucidinostat), induce hyperacetylation of histones and non-histone proteins, leading to growth arrest and programmed cell death [3, 21]. These targets are clinically validated for the treatment of peripheral T-cell lymphoma and are under investigation for other hematological and solid tumors [8, 14]. Beyond oncology, they are also being explored as therapeutic targets for neurodegenerative and inflammatory conditions due to their broad regulatory roles [7, 12].

Other names

HDAC1HDAC2HDAC3HDAC8HDAC10Histone deacetylase 1Histone deacetylase 2Histone deacetylase 3Histone deacetylase 8Histone deacetylase 10Polyamine deacetylase HDAC10

Inhibition of the enzymatic activity of Class I and Class IIb (HDAC10) histone deacetylases, leading to hyperacetylation of histones and non-histone proteins, which induces chromatin remodeling, re-expression of silenced genes, cell cycle arrest, and apoptosis.