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
- Fibrosis and DNA repair are crucial factors for cancer development and metastasis. Here, three-component platinum(IV) hybrids with captopril (CTP) and valproic acid (VPA) functional ligands were developed as antiproliferative and antimetastatic agents. These agents exerted effects by inducing DNA damage, suppressing fibrosis and inhibiting DNA repair. Upon activation, the platinum core bound to DNA and caused mitochondria-mediated apoptosis through the Bcl-2/Bax/caspase-3 pathway. The VPA moiety inhibited the key enzyme HDAC3, disrupted DNA-repair by modulating the proteins P-gp, PARP, and PTEN, and further overcame multidrug resistance (MDR). Furthermore, the TGF-β1/Smad2 and MMPs cascades were inhibited by CTP, while tumor inflammation was also inhibited through downregulating COX-2, TNF-α, and IL-6. These combined actions displayed a synergistic role in attenuating tumor fibrosis, and further reversed EMT. In addition, decreased PD-L1 expression and increased infiltration of CD3 and CD8 T cells were observed, leading to the initiation of antitumor immunity in tumors. - Source: PubMed
Publication date: 2026/06/12
Chen YanFeng ShuaiqiLiu ZhifangZhao YannaJi ChunWang Qingpeng - Nuclear receptor corepressor 1 (NCoR1) and silencing mediator of retinoic acid and thyroid hormone (SMRT) are critical regulators that mediate transcriptional repression through histone deacetylation. Despite high structural homology, their distinct roles in the central nervous system remain poorly understood. To elucidate these roles, we generated neuronal-specific NCoR1 or SMRT knockout mice using Snap25-IRES2-Cre mice. Behavioral assessments revealed that while both NCoR1 and SMRT deficiency led to hypoactivity, social deficits, and mild anxiety, NCoR1-deficient mice uniquely exhibited enhanced learning abilities in a visual discrimination task, indicating functional separation in cognitive regulation. This divergence was supported by RNA-sequencing in the amygdala at postnatal day 21 (PND 21), where SMRT deletion upregulated 449 genes, whereas NCoR1 deletion upregulated only 8 genes. Furthermore, we investigated the protein stability of HDAC3, the primary enzymatic partner of these corepressors. At PND 21, HDAC3 levels were significantly reduced in the NCoR1-deficient hippocampus but significantly increased in the SMRT-deficient amygdala. In contrast, HDAC3 levels remained stable in the adult cerebellum and PND 3 cerebrum regardless of corepressor status. Notably, while mice with deletion of both NCoR1 and SMRT exhibit early postnatal lethality, their HDAC3 levels were unchanged compared to controls at PND 3, suggesting that the lethal phenotype is not primarily driven by a systemic loss of HDAC3 protein. Collectively, our findings demonstrate that NCoR1 and SMRT function through independent transcriptional networks and context-dependent regulatory mechanisms. This study highlights the specialized, non-redundant roles of these homologous corepressors in the brain according to developmental stage and region. - Source: PubMed
Publication date: 2026/06/10
Amano IzukiRitter Megan JNinomiya AyaneKawabata-Iwakawa ReikaVierling TaylorCespedes Isabella SalgueroHollenberg Anthony NKoibuchi Noriyuki - Psoriasis is a chronic autoimmune inflammatory dermatosis with a global prevalence exceeding 3%. Available therapeutic approaches for psoriasis, encompassing topical formulations, monoclonal antibodies, and phototherapy, seldom elicit full clinical remission in practice, yet are plagued by exorbitant costs or impractical administration protocols. To enhance the therapeutic efficacy of ferulic acid (FA), a widely used naturally occurring antioxidant, a series of short-chain fatty acids (SCFAs) were selected for the structural modification of FA, thereby endowing the covalent conjugate with enhanced antioxidant activity, as well as potent immunomodulatory and cell cycle regulatory properties. Using an imiquimod (IMQ)-induced psoriasis-like mouse model, pentanoylated ferulic acid methyl ester (PentFAMe) was identified as the most potent candidate compound, exhibiting the highest efficacy. Its therapeutic effects and underlying mechanism were further elucidated through in vivo and in vitro approaches. Compared with the parent compounds, the conjugate PentFAMe exhibits superior and more comprehensive pharmacological activity. The activity of PentFAMe is substantially higher than the individual component likely to be formed in vivo upon hydrolysis. Pentanoic acid alone displays potent anti-proliferative and anti-inflammatory activities via suppression of HDAC3/6 expression. PentFAMe exerts superior effects by inhibiting HDAC3/6 expression, thereby restoring acetylation levels of H3K27 and NF-κB p65. Meanwhile, PentFAMe surpassed ferulic acid in its ability to activate the antioxidant Nrf2 pathway. Furthermore, effective Nrf2 activation inhibited NF-κB phosphorylation, resulting in a notable decrease in proinflammatory cytokine and chemokine expression. PentFAMe, as a component in an oral formulation, is both cost-effective and convenient, offering a novel potential lead compound against psoriasis. - Source: PubMed
Publication date: 2026/06/10
Li ChenxiYang YuanyuanZhang AoHan HangLi XiandengZhang GuojiangChu LongXu BiaoZhang XiaoZhao Qinjian - cGAS overactivation is linked to various inflammatory and autoimmune diseases. Recent studies identify HDACs as critical regulators of cGAS, suggesting that dual cGAS/HDAC inhibition could be a novel therapeutic strategy. Herein, we report the identification of an HDAC/cGAS dual inhibitor, containing a hydroxamic acid moiety. This compound exhibited potent inhibitory activity against human and mouse cGAS (IC: 0.17 and 1.80 μM, respectively) and moderate activity against HDAC3 and HDAC6 (IC: 1.2 and 0.4 μM, respectively). Mechanistically, directly suppresses cGAS activity and increases its acetylation levels via HDAC3 inhibition. This dual-action profile resulted in robust therapeutic efficacy in murine models of inflammatory bowel disease and Aicardi-Goutières syndrome. Collectively, represents the first cGAS/HDAC dual inhibitor, offering a promising lead for further investigation into cGAS-dependent disorders. - Source: PubMed
Publication date: 2026/06/10
Zhou ZihuaChen MingjieLei ShuyueWang MengDing ChunyongSong ZilanTang WeiZhang Ao - Fasting drives metabolic adaptation but also elicits acute cellular stress. How this stress shapes tissue integrity is unknown. Here, we show that in the intestine, fasting depletes growth factor signaling, which triggers cellular stress. This response functions as a tissue quality-control checkpoint that selectively eliminates pre-existing DNA-damaged cells while sparing healthy counterparts. A short-term fast diminishes TGF-β signaling and elicits endoplasmic reticulum (ER) stress, driving DNA-damaged intestinal cells beyond an apoptotic threshold, thereby reducing the inflammatory burden. Mechanistically, loss of TGF-β signaling triggers FBXO22-Cullin1-mediated degradation of the inositol kinase IPMK, leading to depletion of inositol hexaphosphate (InsP₆). InsP₆ loss attenuates HDAC3 activity and initiates coordinated epigenetic and post-translational reprogramming, thereby increasing CDK5RAP3 abundance. Elevated CDK5RAP3 inhibits ribosomal RPL26 UFMylation, thereby amplifying ER stress and selectively licensing apoptosis in DNA-damaged cells. Collectively, fasting disrupts a TGF-β-InsP -HDAC3 axis to drive ER stress-dependent clearance of DNA-damaged cells, enforcing tissue quality control. - Source: PubMed
Publication date: 2026/05/27
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