Target intelligence / Profile preview

Histone deacetylase 1 (HDAC1), Histone deacetylase 2 (HDAC2), Histone deacetylase 3 (HDAC3), Histone deacetylase 4 (HDAC4) (HDAC1, HDAC2, HDAC3, HDAC4)

Target
HDAC1, HDAC2, HDAC3, HDAC4
Molecular classification
Enzyme, Histone modification enzyme, Epigenetic regulator, Zinc-dependent deacetylase
01

Overview

Histone deacetylases 1, 2, 3, and 4 are part of a family of zinc-dependent enzymes that remove acetyl groups from lysine residues on histone and non-histone proteins, leading to condensation of chromatin and transcriptional silencing. HDAC1, HDAC2, and HDAC3 are classified as Class I HDACs, predominantly located in the nucleus and highly involved in corepressor complexes regulating transcription and cell cycle progression. HDAC4 belongs to Class IIa and shuttles between the nucleus and cytoplasm, playing specific roles in tissue development, especially in muscle and bone. Abnormal activity or expression of these enzymes is implicated in the development and progression of numerous diseases, including various cancers and neurodegenerative conditions, making them key drug targets for HDAC inhibitors. When using this grouping for data structuring, it is advisable to treat each HDAC isoform as an individual molecular target for accurate annotation and downstream applications.

Other names
RPD3L1HD1RPD3L2YAF1RPD3-2SMAP45HDACAKIAA0288
02

Mechanism of action

Inhibition of HDAC activity leading to increased acetylation of histones and non-histone proteins; Chromatin relaxation and enhanced transcription of tumor suppressor genes; Induction of cell cycle arrest, apoptosis, and differentiation in cancer cells

03

Biological functions

Transcriptional repressionChromatin remodelingRegulation of gene expressionCell cycle progressionCell differentiationApoptosisDNA damage response
04

Disease associations

Cancer (various types)Neurodegenerative diseasesCardiovascular diseaseInflammationPsychiatric disorders (notably schizophrenia for HDAC1 and HDAC2)Bone-related diseases (notably HDAC3 and HDAC4 in osteoblast/chondrocyte biology)
05

Safety considerations

Off-target toxicity due to broad inhibition of multiple HDAC isoformsHematological toxicity (e.g., thrombocytopenia, neutropenia)Gastrointestinal symptoms (nausea, vomiting, diarrhea)FatigueCardiotoxicity (noted with some HDAC inhibitors)Possible effects on normal development and differentiation
06

Interacting drugs

Vorinostat (SAHA)

6 more in the full profile.

07

Biomarkers

Histone acetylation levels (e.g., acetylation at lysines 9 and 14 on histone H3)HDAC1/HDAC2/HDAC3/HDAC4 expression levels in tumor biopsiesHistone gene signatures in peripheral blood or tumor samples

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