HDAC8
- Known as:
- HDAC8
- Catalog number:
- 000428A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- HDAC8
Related genes to: HDAC8
- Gene:
- HDAC8 NIH gene
- Name:
- histone deacetylase 8
- Previous symbol:
- HDACL1, WTS, MRXS6
- Synonyms:
- RPD3, KDAC8
- Chromosome:
- Xq13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-28
- Date modifiied:
- 2019-02-19
Related products to: HDAC8
Related articles to: HDAC8
- Ewing sarcoma is an aggressive pediatric cancer for which no targeted therapies have been approved. This disease is driven by EWSR1::ETS family fusions that, like most fusion transcription factors, have proven difficult to target directly. Here, we focus on identifying actionable dependencies within the high-risk STAG2-mutant (STAG2-mut) disease subtype of Ewing sarcoma. In STAG2-mut Ewing sarcoma, STAG1 knockout is synthetically lethal but is not readily druggable. Using the Cancer Dependency Map (DepMap), we identify histone deacetylase 8 (HDAC8) as an enriched vulnerability in this molecular context. CRISPR validation and a newly developed HDAC8 degrader, XY-09-36, confirm this selective dependency and suggest increased reliance on HDAC8-mediated cohesin regulation when STAG2 is lost. These findings establish HDAC8 as a context-dependent, pharmacologically accessible vulnerability and outline a framework for discovering rational targets in tumor subtypes where primary drivers are intrinsically hard to drug. - Source: PubMed
Publication date: 2026/08/26
Olaoye OlasunkanmiXiong YuanRillahan Cory DAdane BiniamDiGiovanni GiuliaRoss Kenneth NAlexe GabrielaHoward BrianaKirmani NadiaNowak Radosław PDonovan Katherine AFischer Eric SStegmaier Kimberly - The impact of fast-food components on epigenetic modifications and their implications for immunotherapy in metastatic breast cancer remain inadequately explored. In this study, we investigated the effects of selected fast-food components monosodium glutamate (MSG), acrylamide (AA), sodium sorbate (SS), and sodium nitrite (NaNO) on the expression of the epigenetic enzymes histone deacetylase 8 (HDAC8) and protein arginine methyltransferase 5 (PRMT5), and their role in suppressing immunotherapeutic responses in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Epigenetic modifications upregulate the expression of immune checkpoint proteins, including the integrin-associated transmembrane protein cluster of differentiation 47 (CD47), which enables metastatic cancer cells to evade immune surveillance by inhibiting macrophage-mediated phagocytosis. These modifications also increase the expression of programmed death-ligand 1 (PD-L1), further promoting immune evasion by inducing T-lymphocyte apoptosis. The key objectives of this study were to determine whether (i) fast-food components (AA, MSG, NaNO, and SS) can directly upregulate the epigenetic enzymes HDAC8 and PRMT5 in MDA-MB-231 cells without prior metabolic activation, and (ii) elevated HDAC8 and PRMT5 expression can induce the overexpression of the immune checkpoint proteins CD47 and PD-L1. Our findings reveal that prolonged exposure to MSG, AA, and SS upregulated the expression of epigenetic enzymes HDAC8 and PRMT5, upregulated oncogenic signaling, and enhanced the stemness-associated features in TNBC cells. These changes are associated with enhanced metastasis and reduced immunotherapeutic effects. Interestingly, our studies revealed that the combined presence of CD47 and HDAC8 inhibitors enhanced macrophage-mediated phagocytosis, thereby enabling immune cells to engulf cancer cells, improved the therapeutic response in TNBC, and promoted anticancer activities. These findings emphasize the importance of personalized dietary strategies for improving the efficacy of cancer immunotherapy and support the integration of specific epigenetic inhibitors with immune checkpoint inhibitors to amplify the therapeutic outcomes. - Source: PubMed
Publication date: 2026/08/10
Mukherjee AsmitaJanah PrithaTripathi ArchanaGayen ParamitaSinha Roy Rituparna - - Source: PubMed
Publication date: 2026/08/27
Papakonstantinou EleniNowak MartaPrince Spasenija SavicSoriano DanielGrize LeticiaFrye Björn ChristianFähndrich SebastianKoelzer Viktor HStolz Daiana - Modulating intersecting pathological pathways via multi-target directed ligands (MTDLs) is an active frontier in drug discovery. Herein, we report the design, one-pot synthesis, and characterization of a novel series of functionalized 2-ureido-6-nitrobenzamide derivatives 4-8 in 72-82% yields. Sequential nitration and imidization of phthalic anhydride 1, followed by sulfonylation, afforded the N-cyclic imide 2 and its sulfonyl ester building block 3. Aminolysis of 3 using various amines and hydrazines furnished target compounds 4-8 via a base-catalyzed Lossen rearrangement/addition-nucleophile ring-opening (ANRO) cascade. The structures were characterized using NMR, FT-IR, and mass spectrometry. In silico SwissADME analysis predicted favorable drug-like profiles adhering to Lipinski's Rule of Five. To normalized binding free energies, multi-parameter optimization (MPO) workflow utilizing, AutoDock Vina converted raw docking energies (ΔG) into calculated logarithmic inhibition constants (pK) across ten targets proteins. The validated and predicted heavy-atom poses closely matched reference structures, with RMSD values confirming docking reliability, while 2D interaction diagrams verified conserved of key contacts. Compound 6 emerged as a prioritized multi-target template, with a balanced predicted dual-target profile against HDAC8 and JNK1. Compound 7 was identified as a prioritized in silico multi-target hit against HDAC8 and PIM1. Structural modifications shifted other derivatives toward target-biased profiles, such as building block 3 against GSK-3β and compound 8 against JAK2. Overall, these tunable 2-ureido-6-nitrobenzamide scaffold serves as an in silico prioritization starting point for the rational design of dual-action therapeutics targeting complex oncology and neurodegenerative networks, requiring future in vitro and in vivo validation. - Source: PubMed
Publication date: 2026/08/20
Farouk MahmoudMahmoud SalsabilImran AhamadMahmoud Sama - Histone deacetylase 8 (HDAC8) has emerged as a promising therapeutic target due to its role in epigenetic regulation. In this study, novel non-hydroxamate-based quinoline analogues were designed and explored as HDAC8-selective inhibitors that exhibit nanomolar HDAC8 enzymatic inhibition. Notably, compounds BHC-10 and BHC-13 showed 30 and 42 nM activity, respectively. Compounds exhibiting below 500 nM activity were evaluated for their cellular activity, and two compounds, BHC-2 and BHC-10, showed promising activity in neuroblastoma cell lines (IMR-32 and SH-SY5Y). Based on both enzymatic and cellular assays, compounds BHC-2, BHC-10, and BHC-13 were selected for further evaluation using clonogenic growth assays, apoptosis assays, and cell cycle analysis. Clonogenic assays revealed a significant, dose-dependent reduction in colony formation. Flow cytometry analysis indicated a dose-dependent increase in apoptotic cell populations and induction of cell cycle arrest at the S phase. Mechanistic studies confirmed target engagement through enhanced acetylation of SMC3, as demonstrated by western blot analysis. Additionally, molecular docking analysis provided insights into the binding interactions of these compounds with the HDAC8 protein. Two compounds from the current work, BHC-10 and BHC-13, emerged as more potent and selective than the reference compound B. Together, the current findings establish these compounds as promising HDAC8 modulators with potential for therapeutic development in neuroblastoma. - Source: PubMed
Publication date: 2026/08/18
Bandaru N V M RaoJoshi VandanaSchweipert MarkusChaitanya Kosana SaiSen DharaniMohammed Muzaffar-Ur-RehmanSharma VivekAbbineni ChandrasekharMeyer-Almes Franz-JosefGowri Chandra Sekhar Kondapalli Venkata