Histone deacetylase 1 and Histone deacetylase 6 (HDAC1/6)

Histone deacetylase 1 (HDAC1) and Histone deacetylase 6 (HDAC6) are essential enzymes that regulate cellular function by removing acetyl groups from lysine residues on both histone and non-histone proteins (UniProt Q13547, Q9UBN7). HDAC1, a Class I deacetylase, is primarily localized in the nucleus where it serves as a core component of transcriptional repressor complexes, such as NuRD and Sin3, to modulate gene expression, cell cycle progression, and DNA damage responses (PubMed: 16762839, NIH). In contrast, HDAC6 is a Class IIb deacetylase predominantly found in the cytoplasm, distinguished by its two functional catalytic domains and its ability to regulate non-histone substrates like alpha-tubulin and HSP90, which are critical for cytoskeletal organization, intracellular transport, and protein homeostasis (PubMed: 12024216, NIH). The dysregulation of these enzymes is strongly linked to the pathogenesis of various cancers, including multiple myeloma and lymphoma, as well as neurodegenerative conditions like Alzheimer's disease (NIH, GeneCards). Therapeutic strategies often involve the use of pan-HDAC inhibitors or isoform-selective agents to restore acetylation balance, thereby inducing apoptosis and inhibiting tumor growth (PubMed: 1.4.2, 1.3.3). However, the clinical application of these inhibitors is frequently challenged by significant safety concerns, most notably hematological toxicities such as thrombocytopenia and gastrointestinal side effects (NIH).

Other names

HD1RPD3L1GON-10CPBHMHD6JM21Protein deacetylase HDAC1Protein deacetylase HDAC6

Inhibition of the zinc-dependent catalytic domains of HDAC1 and HDAC6, preventing the removal of acetyl groups from lysine residues on histones and non-histone proteins. This leads to hyperacetylation, which promotes chromatin relaxation and altered gene transcription (via HDAC1) and disrupts cytoplasmic processes such as microtubule-dependent transport and chaperone-mediated protein folding (via HDAC6).