Ask about this productRelated genes to: HDAC3 Blocking Peptide
- Gene:
- HDAC3 NIH gene
- Name:
- histone deacetylase 3
- Previous symbol:
- -
- Synonyms:
- RPD3, HD3, RPD3-2, KDAC3
- Chromosome:
- 5q31.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-29
- Date modifiied:
- 2019-02-19
Related products to: HDAC3 Blocking Peptide
Related articles to: HDAC3 Blocking Peptide
- Tumor immune evasion is a pivotal mechanism driving therapeutic resistance and poor prognosis in lung cancer. The interleukin-20 receptor β subunit (IL20RB) is implicated in chronic inflammation and oncogenesis, but its precise function and molecular basis in non-small cell lung cancer (NSCLC) require elucidation. - Source: PubMed
Publication date: 2026/08/31
Wang YanghaoLi GuoyuWang WeizhouZhang HengruiZhang YuDeng YajieMu SirongYuan SiyuTu YulinNi JiayiHe YongwenBian Li - Xenophagy is a selective autophagy process crucial for eliminating intracellular pathogens, yet its regulatory mechanisms remain poorly defined. In this study, acetylome profiling identifies dynamic acetylation of the xenophagy receptor NDP52 at K202, and its deacetylation enhances during Salmonella Typhimurium infection. Acetyltransferase CREBBP/KAT3A and deacetylase HDAC3 reciprocally regulate NDP52 K202 acetylation. Deacetylated NDP52 binds more strongly to ATG8 family proteins (MAP1LC3A/B and GABARAPL2), promotes autophagosome-lysosome fusion and pathogen degradation. Innate immune kinase TBK1 phosphorylates HDAC3 at S424, stabilizes it by inhibiting ubiquitination-dependent degradation, and this regulatory cascade links innate immunity to xenophagy. Liver-specific overexpression of deacetylation-mimetic NDP52 in mice reduces hepatic Salmonella Typhimurium burden, attenuates liver necrosis, and suppresses proinflammatory cytokines. This study uncovers a post-translational modification paradigm in xenophagy, where NDP52 acetylation dynamics fine-tune receptor function in antibacterial responses, highlighting the HDAC3-NDP52 axis as a potential therapeutic target for infectious diseases. - Source: PubMed
Publication date: 2026/09/02
Sun WeixiaWang LuqingZhu YifeiZhou YeYing LingxuanYang WenlanLiu ChenJiang XiaoxueLi XieCheng Xiawei - Interferon (IFN) signaling plays a pivotal role in orchestrating antitumor immunity and shaping the response to immune checkpoint blockade (ICB). Although genetic alterations that impair the IFN pathway have been reported, such events are relatively rare, suggesting a potential contribution of epigenetic dysregulation. Here, we identified a RUNX2-mediated epigenetic mechanism that disrupts the type I interferon (IFN-I) signaling pathway in osteosarcoma (OS), thereby limiting the efficacy of ICB. Development of an algorithm to assess the association of 1,425 transcription factors with IFN pathway activation in human OS tumors enabled identification of RUNX2 as a potential negative regulator of IFN signaling. RUNX2 depletion in OS cells activated the IFNB1-driven IFN-I response. Mechanistically, RUNX2 formed a transcriptional repressor complex with NCOR1 and HDAC3 that reduced H3K9 acetylation at the enhancers of key IFN-I genes, leading to their downregulation. Inhibition of the RUNX2-NCOR1-HDAC3 complex enhanced IFN-I signaling, with cGAS, STING, and IFNB1 being required for the induction of interferon-stimulated genes and tumor suppression. Paradoxically, reactivation of IFN-I signaling also upregulated immune checkpoint molecules PD-L1 and PD-L2. Combination treatment with a selective HDAC3 inhibitor and anti-PD-1 antibody led to durable tumor regression in syngeneic OS mouse models, accompanied by increased cytotoxic T cell infiltration. These findings reveal a mechanistic link between RUNX2-driven epigenetic repression and impaired antitumor immunity via the cGAS-STING-IFN-I axis and suggest a rational combinatorial strategy to overcome OS resistance to ICB. - Source: PubMed
Publication date: 2026/09/01
Wang ShashaYan HualongMondal PayelAyaz GamzeYang Howard HKim Young-ImTran Andy DKruhlak Michael Jdu Bois WendyLee Maxwell PHuang Jing - Ischemic stroke (IS) remains a leading cause of global disability and mortality, with limited effective anti-inflammatory interventions. Targeting histone deacetylase 3 (HDAC3) to reprogram microglial polarization holds great therapeutic promise, but the HDAC3-specific inhibitor RGFP966 suffers from poor blood-brain barrier (BBB) penetration and systemic toxicity. Herein, we developed a pH-responsive brain-targeted lipid nanoparticle (CD-TLNP@RGFP966) by integrating T7 peptide modification for BBB transcytosis and cinnamaldehyde-α-cyclodextrin (CA-αCD) encapsulation for acidic lesion-triggered drug release. CD-TLNP@RGFP966 exhibited favorable colloidal stability, biosafety, and pH-dependent release behavior. It efficiently crossed the BBB, accumulated in ischemic brain tissue, promoted microglial M2 polarization, attenuated neuroinflammation, reduced infarct volume, and improved neurological function in tMCAO mice. This study provides a novel targeted nanocarrier strategy for the anti-inflammatory treatment of IS. - Source: PubMed
Publication date: 2026/07/16
Liu YaqiLuo BiaoXu YunLiu DexiangWang Qiujing - 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