Protein / target
Histone deacetylase 1
Protein at a glance
Biological role
RNA polymerase II core promoter sequence-specific DNA binding
Strongest disease association
Neoplasms
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
View complete UniProt function annotationHide complete annotation
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:16762839, PubMed:17704056, PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:16762839, PubMed:17704056). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:16762839, PubMed:17704056). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). As part of the SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription (PubMed:21041482). Also functions as a deacetylase for non-histone targets, such as NR1D2, RELA, SP1, SP3, STAT3, ZNF76 and TSHZ3 (PubMed:12837748, PubMed:16285960, PubMed:16337145, PubMed:16478997, PubMed:17996965, PubMed:19343227). Deacetylates SP proteins, SP1 and SP3, and regulates their function (PubMed:12837748, PubMed:16478997). Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons (PubMed:19081374). Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation (PubMed:19081374). Deacetylates TSHZ3 and regulates its transcriptional repressor activity (PubMed:19343227). Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B (PubMed:17000776). Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity (PubMed:17996965). Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (By similarity). Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer (By similarity). Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation (By similarity). In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase and delactylase by mediating decrotonylation ((2E)-butenoyl) and delactylation (lactoyl) of histones, respectively (PubMed:28497810, PubMed:35044827)
Subcellular location
Domains and Gene Ontology detail (68)Hide
Gene Ontology
- Cchromatin
- Ccytoplasm
- Ccytosol
- Cheterochromatin
- Chistone deacetylase complex
- Cneuronal cell body
- Cnucleoplasm
- Cnucleus
- CNuRD complex
- Cprotein-containing complex
- Cribonucleoprotein complex
- CSin3-type complex
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Cell proliferation & survival
- ·positive regulation of cell population proliferation
Cell migration
- ·negative regulation of cell migration
Transcriptional regulation
- ·Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-termina…
- ·transcription repressor complex
- ·DNA-binding transcription factor binding
- ·RNA polymerase II cis-regulatory region sequence-specific DNA binding
View underlying pathways (25)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Broader indication categories (1)Hide
Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.
8 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Histone deacetylase 1 inhibitor
Indicated for Lymphoma, T-Cell, Lymphoma, T-Cell, Cutaneous, Neoplasms
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene HDAC1
Gene-level evidence surfaced through the gene HDAC1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
Show all associationsHide all associations
Drug development
14 compounds recorded · 8 approved · 6 in clinical development
View all recorded compounds (10)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Protein degraders — Emerging
Other modalities — Strong
View underlying tractability evidence (10)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- New publicationKetogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy.
- New publicationSuberoylanilide Hydroxamic Acid (SAHA) Is a Driver Molecule of Neuroplasticity: Implication for Neurological Diseases.
- New publicationPhase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat in advanced renal cell carcinoma and other solid tumors.
- New publicationVorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.
- New publicationA phase 1 study of vorinostat maintenance after autologous transplant in high-risk lymphoma.
- New publicationA multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.
- New publicationPhase II trial of vorinostat in advanced melanoma.
- New publicationVorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial.
- New publicationPhase I and pharmacokinetic study of the oral histone deacetylase inhibitor vorinostat in Japanese patients with relapsed or refractory cutaneous T-cell lymphoma.
- New publicationEvaluation of safety, pharmacokinetics, and efficacy of vorinostat, a histone deacetylase inhibitor, in the treatment of gastrointestinal (GI) cancer in a phase I clinical trial.
- New publicationEvaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma.
- New publicationA single supratherapeutic dose of vorinostat does not prolong the QTc interval in patients with advanced cancer.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.