HDAC6 histone deacetylase 6
ENSG00000094631 · protein coding · Open Targets profile
Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:38534334, PubMed:39567688). Plays a central role in microtubule- dependent cell motility by mediating deacetylation of tubulin (PubMed:12024216, PubMed:20308065, PubMed:26246421). Required for cilia disassembly via deacetylation of alpha-tubulin (PubMed:17604723, PubMed:26246421). Alpha-tubulin deacetylation results in destabilization of dynamic microtubules (By similarity). Promotes deacetylation of CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141). Deacetylates SQSTM1 (PubMed:31857589). Deacetylates peroxiredoxins PRDX1 and PRDX2, decreasing their reducing activity (PubMed:18606987). Deacetylates antiviral protein RIGI in the presence of viral mRNAs which is required for viral RNA detection by RIGI (By similarity). Sequentially deacetylates and polyubiquitinates DNA mismatch repair protein MSH2 which leads to MSH2 degradation, reducing cellular sensitivity to DNA-damaging agents and decreasing cellular DNA mismatch repair activities (PubMed:24882211). Deacetylates DNA mismatch repair protein MLH1 which prevents recruitment of the MutL alpha complex (formed by the MLH1-PMS2 heterodimer) to the MutS alpha complex (formed by the MSH2-MSH6 heterodimer), leading to tolerance of DNA damage (PubMed:30770470). Deacetylates RHOT1/MIRO1 which blocks mitochondrial transport and mediates axon growth inhibition (By similarity). Deacetylates transcription factor SP1 which leads to increased expression of ENG, positively regulating angiogenesis (PubMed:38534334). Deacetylates KHDRBS1/SAM68 which regulates alternative splicing by inhibiting the inclusion of CD44 alternate exons (PubMed:26080397). Deacetylates PRDM16 (By similarity). Acts as a valine sensor by binding to valine through the primate-specific SE14 repeat region (PubMed:39567688). In valine deprivation conditions, translocates from the cytoplasm to the nucleus where it deacetylates TET2 which promotes TET2-dependent DNA demethylation, leading to DNA damage (PubMed:39567688). Promotes odontoblast differentiation following IPO7-mediated nuclear import and subsequent repression of RUNX2 expression (By similarity). In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome (PubMed:17846173). Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and targets them to the aggresome, facilitating their clearance by autophagy (PubMed:17846173). Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer (PubMed:24413532). {ECO:0000250|UniProtKB:D3ZVD8, ECO:0000250|UniProtKB:Q9Z2V5, ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:18606987, ECO:0000269|PubMed:20308065, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:24882211, ECO:0000269|PubMed:26080397, ECO:0000269|PubMed:26246421, ECO:0000269|PubMed:30538141, ECO:0000269|PubMed:30770470, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:38534334, ECO:0000269|PubMed:39567688}.
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
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.05625399947166443 (upper bound 0.11828000098466873). 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 HDAC6 (belinostat, givinostat, romidepsin, entinostat, panobinostat lactate, vorinostat, panobinostat, tacedinaline, abexinostat, ricolinostat, fimepinostat, quisinostat), 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
- Bristol-Myers SquibbBristol-Myers Squibb · 2 of 2 trials Phase 2+
- 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
- Jennifer E AmengualYale University Cancer Center LAO · 1 of 2 trials Phase 2+
- 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+
Registry trials of belinostat, givinostat, romidepsin, entinostat, panobinostat lactate, vorinostat, panobinostat, tacedinaline, abexinostat, ricolinostat, fimepinostat, quisinostat 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.
203 trials of drugs against HDAC6 were stopped early; 35 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of belinostat, givinostat, romidepsin, entinostat, panobinostat lactate, vorinostat, panobinostat, tacedinaline, abexinostat, ricolinostat, fimepinostat, quisinostat, 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 203.
- 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 · 2025-03-04 · Celgene · ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone“Change in business priorities.”
- 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”
Paediatric incentives and obligations for HDAC6's drugs
For belinostat, givinostat, romidepsin, entinostat, panobinostat lactate, vorinostat, panobinostat, tacedinaline, abexinostat, ricolinostat, fimepinostat, quisinostat: 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 · HDAC6 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; +10 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 belinostat, givinostat, romidepsin, entinostat, panobinostat lactate, vorinostat, panobinostat, tacedinaline, abexinostat, ricolinostat, fimepinostat, quisinostatRule: 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 · 84 interventional studies of belinostat, givinostat, romidepsin, entinostat, panobinostat lactate, vorinostat, panobinostat, tacedinaline, abexinostat, ricolinostat, fimepinostat, quisinostat include patients under 18; 21 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.