HDAC3 histone deacetylase 3
ENSG00000171720 · protein coding · Open Targets profile
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:21030595, PubMed:21444723, PubMed:23911289, PubMed:25301942, PubMed:28167758, PubMed:28497810, PubMed:32404892, PubMed:22230954). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes, such as N-Cor repressor complex, which activate the histone deacetylase activity (PubMed:23911289, PubMed:22230954). Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity). During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Also functions as a deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA and STAT3 (PubMed:15653507, PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28167758). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl), 2-hydroxyisobutanoyl (2- hydroxyisobutyryl) and isonicotinyl acyl groups from lysine residues, leading to protein decrotonylation, delactylation, de-2- hydroxyisobutyrylation and deisonicotinylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293, PubMed:34545082, PubMed:35044827). Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293). Mediates delactylation NBN/NBS1, thereby inhibiting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38961290). {ECO:0000250|UniProtKB:O88895, ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21444723, ECO:0000269|PubMed:22230954, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:32404892, ECO:0000269|PubMed:34545082, ECO:0000269|PubMed:34608293, ECO:0000269|PubMed:35044827, ECO:0000269|PubMed:38961290}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- GO CC high conf
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.3370699882507324 (upper bound 0.4853900074958801). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 183 registry trials, updated in the last three years, of the most advanced drugs against HDAC3 (romidepsin, givinostat, vorinostat, entinostat, belinostat, panobinostat lactate, panobinostat, tacedinaline, abexinostat, mocetinostat, quisinostat, fimepinostat), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Yuankai SHICancer Institute and Hospital, Chinese Academy of Medical Sciences · 3 of 3 trials Phase 2+Ph2NCT03936153 · Study to Evaluate Efficacy and Safety of Oral Abexinostat in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)brief
- Steven HorwitzMemorial Sloan Kettering Cancer Center · 2 of 3 trials Phase 2+
- Yago L NietoM.D. Anderson Cancer Center · 2 of 3 trials Phase 2+Ph1NCT03259503 · Olaparib and High-Dose Chemotherapy in Treating Patients With Relapsed or Refractory Lymphomas Undergoing Stem Cell Transplantbrief
- David SiegelHackensack Meridian Health · 2 of 2 trials Phase 2+
- Juan C RamosUniversity of Miami · 2 of 2 trials Phase 2+
- Vered StearnsSidney Kimmel Comprehensive Cancer Center at Johns Hopkins · 2 of 2 trials Phase 2+
- Roisin M ConnollyECOG-ACRIN Cancer Research Group · 1 of 3 trials Phase 2+Ph3NCT02115282 · Exemestane With or Without Entinostat in Treating Patients With Recurrent Hormone Receptor-Positive Breast Cancer That is Locally Advanced or Metastaticbrief
- Nilofer AzadJohns Hopkins University · 1 of 2 trials Phase 2+
- Ahmad TarhiniMoffitt Cancer Center · 1 of 1 trials Phase 2+
- Alessandro RambaldiAzienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy · 1 of 1 trials Phase 2+
- Alexander N ShoushtariMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Alison MoskowitzMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Amelia InsaMedical Oncology Service. Hospital Clínico Universitario - Valencia (Spain) · 1 of 1 trials Phase 2+
- Andrew ZelenetzMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Bertomeu MassuttiMedical Oncology Service. General Hospital. Alicante. Spain · 1 of 1 trials Phase 2+
Registry trials of romidepsin, givinostat, vorinostat, entinostat, belinostat, panobinostat lactate, panobinostat, tacedinaline, abexinostat, mocetinostat, quisinostat, fimepinostat updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 142 of 177 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 6 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
209 trials of drugs against HDAC3 were stopped early; 36 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of romidepsin, givinostat, vorinostat, entinostat, belinostat, panobinostat lactate, panobinostat, tacedinaline, abexinostat, mocetinostat, quisinostat, fimepinostat, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 209.
- suspended · 2026-10-22 · Children's Hospital Medical Center, Cincinnati · matched by the registry's drug synonyms“This study will be closing at CCHMC and may be transferred to a principal investigator at another insitutiton.”
- suspended · 2026-09-22 · University of North Carolina, Chapel Hill · Vorinostat“Study was put on pause on July 29, 2026, due to a Grade 5 Serious adverse event”
- terminated · 2026-09-21 · Institut Claudius Regaud · Zolinza (vorinostat), vinorelbineNo reason given
- terminated · 2026-09-16 · Jennifer Amengual · Romidepsin“Lack of funding and recruitment complications caused by COVID-19”
- terminated · 2026-09-04 · University of Utah · Belinostat“No accrual in one year”
- withdrawn · 2026-05-18 · Virogen Biotechnology Inc. · Vorinostat“This record is an earlier version (crossover design). After FDA-approved IND sponsor transfer to Virogen, the study was redesigned. This protocol will never start. The new protocol is NCT07529405.”
- terminated · 2026-05-06 · University of Michigan Rogel Cancer Center · Romidepsin“Lack of accrual”
- terminated · 2026-03-03 · National Cancer Institute (NCI) · Belinostat“Drug supply issues”
- terminated · 2026-03-02 · Antonio Fojo · Entinostat“Lack of funding and drug supply”
- terminated · 2026-01-30 · National Cancer Institute (NCI) · Belinostat“Other - Adverse Events”
- withdrawn · 2025-09-11 · Judit Pich · matched by the registry's drug synonyms“The clinical trial was discontinued prior to initiation due to the withdrawal of the vaccine manufacturer (etherRNA) from the research consortium. As a result, the study could not proceed as originally planned.”
- terminated · 2025-06-08 · Columbia University · Panobinostat 15 MG“FDA withdrew approval of the new drug application (NDA) for panobinostat as of March 24, 2022 because it was not feasible for the company to complete the required postmarketing clinical trials.”
- terminated · 2025-05-26 · Mayo Clinic · Belinostat, Romidepsin“funding - sponsor filing Chapter 11 bankruptcy”
- terminated · 2025-05-16 · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · Romidepsin“Closed by Sponsor”
- terminated · 2025-05-02 · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · Panobinostat“Arm A - reached goal; Arm B - poor accrual”
- withdrawn · 2025-04-15 · National Institute of Neurological Disorders and Stroke (NINDS) · Vorinostat“Lack of enrollment.”
- withdrawn · 2025-04-04 · Case Comprehensive Cancer Center · Vorinostat“PI left”
- terminated · 2025-03-20 · Roberto Pili · Entinostat“Genentech has closed the study due to lack of data with Atezo”
- terminated · 2025-03-07 · Spanish Lung Cancer Group · Vorinostat plus ErlotinibNo reason given
- terminated · 2025-02-24 · Australian & New Zealand Children's Haematology/Oncology Group · Panobinostat“Drug supply”
- terminated · 2025-02-10 · Biodexa Pharmaceuticals · matched by the registry's drug synonyms“Strategic decision”
- terminated · 2024-11-12 · National Cancer Institute (NCI) · Vorinostat“CTEP Initiated Action”
- withdrawn · 2024-10-15 · Virginia Commonwealth University · Vorinostat Oral Capsule Group 1, Vorinostat Oral Capsule Group 2“PIs were unable to recruit any participants”
- terminated · 2024-09-03 · Roberto Pili · Entinostat“Funder halted development of compound in this disease”
- terminated · 2024-08-22 · M.D. Anderson Cancer Center · Vorinostat“No Sponsor funding for continuation of trial”
Paediatric incentives and obligations for HDAC3's drugs
For romidepsin, givinostat, vorinostat, entinostat, belinostat, panobinostat lactate, panobinostat, tacedinaline, abexinostat, mocetinostat, quisinostat, fimepinostat: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · HDAC3 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000223656 (givinostat, Treatment of polycythaemia vera): W: decision granting a waiver in all age groups for all conditions or indications, 3 Jan 2025; EMEA-000551-PIP04-21-M03 (givinostat, Treatment of Duchenne muscular dystrophy): PM: decision on the application for modification of an agreed PIP, 8 Mar 2024; EMEA-001023-PIP01-10 (romidepsin, Treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated)): W: decision granting a waiver in all age groups for all conditions or indications, 3 Feb 2011; EMEA-000805-PIP01-09 (vorinostat, Malignant pleural mesothelioma;Treatment of Cutaneous T-Cell Lymphoma): W: decision granting a waiver in all age groups for all conditions or indications, 30 Apr 2010; +1 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/12/1063 expired 8 Nov 2012: Treatment of multiple myeloma; EU/3/12/1009 positive 4 Jul 2012: Treatment of Duchenne muscular dystrophy; EU/3/10/732 positive 10 Jun 2010: Treatment of Hodgkin's lymphoma; EU/3/22/2660 withdrawn 18 Jul 2022: Treatment of glioma; +12 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Duvyzat: authorised since 6 Jun 2025, orphan medicine, conditional; Farydak: authorised since 28 Aug 2015; Istodax: refused, orphan medicine; Vorinostat MSD: application withdrawnRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of romidepsin, givinostat, vorinostat, entinostat, belinostat, panobinostat lactate, panobinostat, tacedinaline, abexinostat, mocetinostat, quisinostat, fimepinostatRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 85 interventional studies of romidepsin, givinostat, vorinostat, entinostat, belinostat, panobinostat lactate, panobinostat, tacedinaline, abexinostat, mocetinostat, quisinostat, fimepinostat include patients under 18; 22 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 14 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.