Histone deacetylase 6 (HDAC6)
histone deacetylase 6 (HDAC6) is a cytoplasmic histone deacetylase and a member of the class IIb HDAC family.
histone deacetylase 6 (HDAC6) is a cytoplasmic histone deacetylase and a member of the class IIb HDAC family. Unlike many other HDACs that primarily regulate chromatin in the nucleus, HDAC6 is best known for deacetylating non-histone substrates in the cytoplasm, thereby influencing processes such as protein quality control, intracellular transport, stress responses, and cell signaling. Because of these functions, HDAC6 has attracted substantial interest as a therapeutic target in cancer, neurodegenerative disease, inflammatory disorders, and metabolic disease.
Biologically, HDAC6 is often discussed as a regulator of proteostasis and cellular stress pathways. In recent research, it has been linked to stress granule biology through deacetylation of G3BP1, to neuronal and pain-related signaling in brain regions such as the central amygdala and parabrachial nuclei, and to disease-relevant pathways involving β-tubulin (TUBB), BCL2 apoptosis regulator, and Cyclooxygenase 2 (COX-2). Its selective inhibition is being explored as a strategy to modulate disease phenotypes while potentially avoiding some of the broader effects associated with class I HDAC inhibition.
Where the papers sit
16 papers from the last 6 months study Histone deacetylase 6 (HDAC6) directly · updated from PubMed 7 Oct 2026
Study type 0 clinical trials · 16 preclinical
Themes one subject · 1 new direction
Those 16 are all about one subject.
-
HDAC6 Therapeutic Targeting
Selective HDAC6 inhibitors and PROTAC degraders are being developed across cancer, neurodegeneration, infection, and autoimmune disease. Dual- and triple-target agents pair HDAC6 inhibition with STAT3, cGAS, or NQO1 blockade, while single-target compounds are linked to apoptosis, autophagy disruption, and improved microtubule trafficking. Evidence remains predominantly preclinical, with activity shown in cell and animal models. The key open question is whether selectivity and degradation can translate into safe clinical therapies.
HDAC6 is a reciprocal modification partner in a ciliary-disassembly feedback loop during diabetic complications
Hyperglycemic stress in diabetic retinopathy and nephropathy revealed that HDAC6 is not merely a downstream deacetylase or therapeutic target, as in the inhibitor studies, but a component of a self-reinforcing regulatory complex with PRMT1 at the ciliary basal body. PRMT1 methylated HDAC6 at arginine 16 to increase its stability, while HDAC6 deacetylated PRMT1 at lysine 128 to elevate PRMT1 levels; genetic ablation of either enzyme preserved ciliary architecture and organ function in diabetic mice. This assigns HDAC6 a previously unrepresented role as one half of a reciprocal methylation–deacetylation circuit that stabilizes a pathological pro-disassembly complex, changing the mechanistic interpretation of its contribution to diabetic tissue injury 42691060Sep.
Papers
The 16 papers from the last 6 months that study Histone deacetylase 6 (HDAC6) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
HDAC6 Therapeutic Targeting (16)
- Targeting the DNHD1-HDAC6 axis inactivates prostate cancer cell aggressiveness in vitro, suggesting potential therapeutic vulnerability. Oncology reports · 2 Oct 2026 PMID 42825379
- Rapid Two-Step Multicomponent Synthesis and Structure-degradation Relationships of Selective HDAC6 PROTAC Degraders. Journal of medicinal chemistry · 10 Sept 2026 PMID 42720482
- Machine Learning and Molecular Modeling Reveal HDAC6 as a Key Target of Tanshinone IIA in Multiple Myeloma. The journal of physical chemistry. B · 3 Sept 2026 PMID 42691419
- Hyperglycemic stress aggravates diabetic retinopathy and nephropathy by promoting cilium disassembly via a deacetylation- and methylation-mediated regulatory mechanism. PLoS biology · 3 Sept 2026 PMID 42691060
- Design, synthesis, and biological evaluation of selective HDAC6 inhibitors featuring an N-benzyl-2-(aryl/heteroaryl)acetamide cap. Bioorganic chemistry · 27 Aug 2026 PMID 42660046
- HDAC6 inhibition reduces Pseudomonas aeruginosa adherence and internalization in cystic fibrosis epithelial cells via microtubule stabilization. Infection and immunity · 12 Aug 2026 PMID 42584415
- Design, synthesis, and evaluation of anti-solid-tumor activity of niclosamide-based STAT3/HDAC dual-target inhibitors. Bioorganic chemistry · 29 Jul 2026 PMID 42526131
- HDAC6 inhibition alleviates mitochondrial trafficking in models of Charcot-Marie-Tooth disease type 2A. JCI insight · 14 Jul 2026 PMID 42446926
- Discovery of Effective Dual PROTAC Degraders with Synergistic Antitumor Activity for Overcoming Tamoxifen-Resistant Breast Cancer. Journal of medicinal chemistry · 7 Jul 2026 PMID 42411996
- Taginostat, a new quinolone-based HDAC6 inhibitor, promotes apoptosis of chronic lymphocytic leukemia cells in vitro and in vivo by activating STAT4. Apoptosis : an international journal on programmed cell death · 4 Jul 2026 PMID 42400850
- Discovery of novel NQO1/STAT3/HDAC triple-target agents for the treatment of triple negative breast cancer. Bioorganic chemistry · 24 Jun 2026 PMID 42341572
- Selective HDAC6 inhibition perturbs autophagy and enhances integrated stress response-mediated immunogenic apoptosis in chronic myeloid leukemia. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 12 Jun 2026 PMID 42284888
- Design, Synthesis, and Pharmacological Evaluation of cGAS/HDAC Dual Inhibitors for Treatment of Autoimmune Diseases. Journal of medicinal chemistry · 10 Jun 2026 PMID 42268702
- Thiazole-Linked N-Hydroxypropanamide Derivatives: Selective HDAC6 Inhibitors with Therapeutic Potential for Neurodegenerative Diseases. Journal of medicinal chemistry · 4 Jun 2026 PMID 42241502
- Development of novel quinoline derivatives as selective HDAC6 inhibitors exhibiting multiple anticancer effects. Bioorganic chemistry · 29 May 2026 PMID 42214832
- Development of Biphenyl-Substituted Uracil-Based Hydroxamic Acids (UBHAs) as Potent HDAC Inhibitors with Pro-Apoptotic Activity in Leukemia and Prostate Cancer Cells. Journal of medicinal chemistry · 30 Apr 2026 PMID 42059134
By study type
Preclinical: animal, cell and lab studies (16)
- Targeting the DNHD1-HDAC6 axis inactivates prostate cancer cell aggressiveness in vitro, suggesting potential therapeutic vulnerability. Oncology reports · 2 Oct 2026 PMID 42825379
- Rapid Two-Step Multicomponent Synthesis and Structure-degradation Relationships of Selective HDAC6 PROTAC Degraders. Journal of medicinal chemistry · 10 Sept 2026 PMID 42720482
- Machine Learning and Molecular Modeling Reveal HDAC6 as a Key Target of Tanshinone IIA in Multiple Myeloma. The journal of physical chemistry. B · 3 Sept 2026 PMID 42691419
- Hyperglycemic stress aggravates diabetic retinopathy and nephropathy by promoting cilium disassembly via a deacetylation- and methylation-mediated regulatory mechanism. PLoS biology · 3 Sept 2026 PMID 42691060
- Design, synthesis, and biological evaluation of selective HDAC6 inhibitors featuring an N-benzyl-2-(aryl/heteroaryl)acetamide cap. Bioorganic chemistry · 27 Aug 2026 PMID 42660046
- HDAC6 inhibition reduces Pseudomonas aeruginosa adherence and internalization in cystic fibrosis epithelial cells via microtubule stabilization. Infection and immunity · 12 Aug 2026 PMID 42584415
- Design, synthesis, and evaluation of anti-solid-tumor activity of niclosamide-based STAT3/HDAC dual-target inhibitors. Bioorganic chemistry · 29 Jul 2026 PMID 42526131
- HDAC6 inhibition alleviates mitochondrial trafficking in models of Charcot-Marie-Tooth disease type 2A. JCI insight · 14 Jul 2026 PMID 42446926
- Discovery of Effective Dual PROTAC Degraders with Synergistic Antitumor Activity for Overcoming Tamoxifen-Resistant Breast Cancer. Journal of medicinal chemistry · 7 Jul 2026 PMID 42411996
- Taginostat, a new quinolone-based HDAC6 inhibitor, promotes apoptosis of chronic lymphocytic leukemia cells in vitro and in vivo by activating STAT4. Apoptosis : an international journal on programmed cell death · 4 Jul 2026 PMID 42400850
- Discovery of novel NQO1/STAT3/HDAC triple-target agents for the treatment of triple negative breast cancer. Bioorganic chemistry · 24 Jun 2026 PMID 42341572
- Selective HDAC6 inhibition perturbs autophagy and enhances integrated stress response-mediated immunogenic apoptosis in chronic myeloid leukemia. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 12 Jun 2026 PMID 42284888
- Design, Synthesis, and Pharmacological Evaluation of cGAS/HDAC Dual Inhibitors for Treatment of Autoimmune Diseases. Journal of medicinal chemistry · 10 Jun 2026 PMID 42268702
- Thiazole-Linked N-Hydroxypropanamide Derivatives: Selective HDAC6 Inhibitors with Therapeutic Potential for Neurodegenerative Diseases. Journal of medicinal chemistry · 4 Jun 2026 PMID 42241502
- Development of novel quinoline derivatives as selective HDAC6 inhibitors exhibiting multiple anticancer effects. Bioorganic chemistry · 29 May 2026 PMID 42214832
- Development of Biphenyl-Substituted Uracil-Based Hydroxamic Acids (UBHAs) as Potent HDAC Inhibitors with Pro-Apoptotic Activity in Leukemia and Prostate Cancer Cells. Journal of medicinal chemistry · 30 Apr 2026 PMID 42059134
Written from 16 PubMed abstracts, each one listed by PMID above. Published: 2026-06-15. Last written: 2026-09-12 by GPT. Drafted by language models from published abstracts; not medical advice.