Human HDAC6 Active Enzyme
- Known as:
- Human HDAC6 Active Enzyme
- Catalog number:
- x1740e
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Exalpha
- Gene target:
- Human HDAC6 Active Enzyme
Related genes to: Human HDAC6 Active Enzyme
- Gene:
- HDAC6 NIH gene
- Name:
- histone deacetylase 6
- Previous symbol:
- -
- Synonyms:
- KIAA0901, JM21, HD6, FLJ16239, PPP1R90
- Chromosome:
- Xp11.23
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-28
- Date modifiied:
- 2015-09-11
Related products to: Human HDAC6 Active Enzyme
Related articles to: Human HDAC6 Active Enzyme
- Multiple myeloma (MM) is a malignant blood cancer marked by severe bone destruction and immune microenvironment disruption. Yet relapse and drug resistance remain major clinical challenges. Tanshinone IIA (TIIA) exhibits potent antitumor activity, but its molecular targets and mechanisms in MM remain unclear. Here, we systematically elucidate TIIA's pharmacological mechanisms in MM using network pharmacology, transcriptomics, molecular docking, molecular dynamics (MD) simulations, and in vitro cellular experiments. Histone deacetylase 6 (HDAC6) was identified as a key prognostic target in MM via integrative bioinformatics─combining cross-database analysis, machine learning (LASSO, SVM-RFE, random forest), and survival validation in the MMRF-CoMMpass cohort. Molecular docking and MD simulations showed stable binding of TIIA to HDAC6. In vitro, TIIA directly inhibited HDAC6 enzymatic activity and selectively killed U266 and RPMI 8226 myeloma cells in a dose-dependent manner, with minimal toxicity to normal cells. Additionally, gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) immune profiling using the LM22 signature suggested that HDAC6 participates in microenvironmental remodeling by modulating cell adhesion-mediated resistance and orchestrating an immunosuppressive niche characterized by monocyte depletion. This study highlights for the first time the critical role of HDAC6 in TIIA-mediated antimyeloma activity and provides novel mechanistic insights and potential targeted therapeutic strategies for the treatment of MM. - Source: PubMed
Gao JianChu JiawenLi Pengpeng - Primary cilia are essential microtubule-based sensory organelles, and their dysfunction has been increasingly linked to metabolic stress. However, the underlying molecular mechanisms remain poorly understood. Herein, we reveal that ciliary defects in retinal photoreceptors and renal tubules exacerbate tissue damage during the progression of diabetic complications. Under hyperglycemic stress, protein arginine methyltransferase 1 (PRMT1) and histone deacetylase 6 (HDAC6) are significantly upregulated in both retinal and renal tissues. Genetic ablation of either enzyme effectively preserves ciliary architecture and restores organ function in diabetic mice. Mechanistically, PRMT1 localizes to the basal body, where it interacts with and methylates HDAC6 at arginine 16, consequently enhancing HDAC6 stability. In turn, HDAC6 mediates the deacetylation of PRMT1 at lysine 128, which elevates PRMT1 protein levels. This mutual modification crosstalk establishes a pathological positive feedback loop that stabilizes a pro-disassembly complex at the basal body, thereby potentiating ciliary impairment and expediting the progression of diabetic complications. Pharmacological inhibition of the PRMT1-HDAC6 loop significantly attenuates the pathological features of both diabetic retinopathy and nephropathy. Collectively, our findings uncover a reciprocal regulatory mechanism mediated by deacetylation and arginine methylation that drives cilium disassembly under hyperglycemic stress, providing promising therapeutic targets for the treatment of metabolic ciliopathies. - Source: PubMed
Publication date: 2026/09/03
Ran JieWei ChangfengYang YangZhang YufeiGuo GuizhiMa NanYin LongFan HongjunLi JingruiGuo HengZhang RenshuaiWang RunaLi DengwenLiu Min - Sodium-glucose cotransporter (SGLT) inhibitors are increasingly recognised for anticancer activity beyond their established glycaemic effects. While selective SGLT2 inhibitors have been reported to suppress tumour cell proliferation and modulate AMPK/mTOR and PI3K/AKT signalling, whether dual SGLT1/2 inhibition is associated with modulation of epigenetic regulators has remained largely unexplored. Here, we investigated the anticancer effects of sotagliflozin, a dual SGLT1/2 inhibitor, in breast (MCF-7) and lung (A549) cancer cells. Sotagliflozin reduced cell viability, clonogenic survival, migration, and invasion, and these effects were accompanied by G2/M cell-cycle arrest, increased AMPK activation, and changes in PTEN-AKT-mTOR signalling. Molecular docking analysis predicted favourable interactions between sotagliflozin and DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), with the strongest predicted binding to DNMT1 (-8.9 kcal/mol). Consistent with these computational predictions, sotagliflozin treatment was associated with reduced total DNMT enzymatic activity, decreased DNMT1 mRNA and protein abundance, and reduced protein abundance of class I and class II histone deacetylases (HDAC1-4 and HDAC6) in both cell lines. In addition, sotagliflozin treatment was associated with autophagy-related changes, including increased acidic vesicular organelles together with elevated LC3-II and Beclin-1 protein abundance. Collectively, these findings demonstrate that sotagliflozin exerts broad anticancer effects in breast and lung cancer cells and provide preliminary evidence that its treatment is associated with modulation of DNMT1 and HDAC expression. Further studies are required to determine whether these epigenetic changes contribute directly to the observed cellular responses or represent downstream consequences of metabolic perturbation. - Source: PubMed
Hima P KAswathy KDuddukuri Govinda Rao - Histone deacetylase 6 (HDAC6) is predominantly localized in the cytoplasm with nucleocytoplasmic shuttling capability. Featuring two tandem catalytic domains and a C-terminal ubiquitin-binding domain, it primarily deacetylates non-histone substrates such as α-tubulin and HSP90. This distinct subcellular localization and substrate profile endow HDAC6 with the unique capacity to orchestrate pivotal roles in cytoskeletal regulation, the cellular stress response, protein degradation, and cell migration, thereby positioning it as a highly attractive target for anti-tumor drug development. Utilizing the previously identified hit compound Hit-063 as a starting point and guided by the classic HDAC inhibitor pharmacophore model, a series of novel compounds incorporating an N-benzyl-2-(aryl/heteroaryl)acetamide fragment were rationally designed and synthesized. Among these analogs, compound 27 (Cmpd_27) was identified as the most promising lead, exhibiting potent nanomolar inhibition against HDAC6 with an IC value of 4.29 ± 0.12 nM. Notably, Cmpd_27 demonstrated superior isoform selectivity, with selectivity indices exceeding 150-fold over HDAC1 and HDAC3, as further validated by Western blot analysis. At the cellular level, Cmpd_27 triggered G2/M phase arrest and induced apoptosis in HCT-116 cells, leading to a significant suppression of cell proliferation (IC = 0.69 ± 0.04 μM). Moreover, insights derived from quantum chemical analysis of frontier molecular orbitals and molecular dynamics (MD) simulations provide a robust theoretical foundation for the rational design and structural optimization of next-generation selective HDAC6 inhibitors. - Source: PubMed
Publication date: 2026/08/22
Li TingtingWei LingfangShi HeYan WenyingSun YujieZhang YushaWang YitengLu XiangyuFu YanLiu ZhaoboYuan PingfanLiu JieZhang YangJia QingzhongLi Xuedong - Major depressive disorder (MDD) is a heterogeneous psychiatric disorder characterized by impaired mood, neuroplasticity, neuroinflammation, and dysregulated stress response systems. Chronic stress can induce epigenetic changes leading to depression. Evidence suggests that histone acetylation and deacetylation are epigenetic processes involved in changes in gene expression. Histone deacetylases (HDACs) modulate chromatin structure and transcription, and their dysregulation is associated with stress susceptibility, decreased brain-derived neurotrophic factor (BDNF) signaling, impaired synaptic plasticity, and inflammatory activation. HDAC isoforms HDAC3 and HDAC6 have emerged as epigenetic regulators in stress-induced depression. HDAC3 is a transcriptional regulator involved in neuroplasticity-related gene expression, inflammatory signaling, and glucocorticoid receptor-mediated stress responses. In contrast, HDAC6 is cytoplasmic and regulates non-histone substrates involved in microtubule dynamics, synaptic function, protein trafficking, and the regulation of the hypothalamic-pituitary-adrenal axis (HPA axis). Preclinical studies show that HDAC3 or HDAC6 inhibition can exert antidepressant-like effects by promoting neuroplasticity, reducing neuroinflammation, and restoring stress-related signaling. Dual targeting is an interesting therapeutic approach because both regulate complementary mechanisms. However, clinical translation is limited by poor blood-brain barrier penetration, systemic toxicity, insufficient isoform selectivity, and a lack of clinical evidence. This review summarizes the roles and mechanisms of HDAC3 and HDAC6, the rationale for dual targeting, translational limitations, and future therapeutic perspectives. - Source: PubMed
Publication date: 2026/08/16
Mohan Arathy SJayasankar NarayananKashid Vivekanand AnkushPatel Ravish JPrajapati Bhupendra