ArticleEuropean journal of medicinal chemistry2022
Identification of histone deacetylase 10 (HDAC10) inhibitors that modulate autophagy in transformed cells.
Article in European journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- MBind: A Web-Based Platform for Metalloprotein and Nonmetalloprotein Docking with Optional ML Docking Integration.Molecules (Basel, Switzerland) · 2026Article
- Novel selective indole based histone deacetylase 10 inhibitors as anticancer therapeutics.Scientific reports · 2025Article
- Unraveling the Catalytic Mechanism and Substrate Selectivity of HDAC10: A Dual-Filter Approach for Polyamine Deacetylation.JACS Au · 2025Article
- Histone deacetylases 10 as a prognostic biomarker correlates with tumor microenvironment and therapy response in colorectal cancer.World journal of gastroenterology · 2025Article
- Development and Characterization of the First Selective Class IIb Histone Deacetylase Degraders.Journal of medicinal chemistry · 2025Article
- Article
- Histone Deacetylase Inhibitors Promote the Anticancer Activity of Cisplatin: Mechanisms and Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Expression, purification, and crystallization of "humanized" Danio rerio histone deacetylase 10 "HDAC10", the eukaryotic polyamine deacetylase.Methods in enzymology · 2025Article
- Design, Synthesis, and Structural Evaluation of Acetylated Phenylthioketone Inhibitors of HDAC10.ACS medicinal chemistry letters · 2024Article
- Elevated N1-Acetylspermidine Levels in Doxorubicin-treated MCF-7 Cancer Cells: Histone Deacetylase 10 Inhibition with an N1-Acetylspermidine Mimetic.Journal of cancer prevention · 2024Article
- HDAC10 inhibition represses melanoma cell growth and BRAF inhibitor resistance via upregulating SPARC expression.NAR cancer · 2024Article
- Novel hydroxamic acid derivative induces apoptosis and constrains autophagy in leukemic cells.Journal of advanced research · 2024Article
- Chemical Versatility in Catalysis and Inhibition of the Class IIb Histone Deacetylases.Accounts of chemical research · 2024Review
- Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression.Cell reports · 2024Article
- Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation.Journal of medicinal chemistry · 2023Article
- Microtubule acetylation dyshomeostasis in Parkinson's disease.Translational neurodegeneration · 2023Review
- Selectivity of Hydroxamate- and Difluoromethyloxadiazole-Based Inhibitors of Histone Deacetylase 6 In Vitro and in Cells.International journal of molecular sciences · 2023Article
- Aza-SAHA Derivatives Are Selective Histone Deacetylase 10 Chemical Probes That Inhibit Polyamine Deacetylation and Phenocopy HDAC10 Knockout.Journal of the American Chemical Society · 2022Article
- First Fluorescent Acetylspermidine Deacetylation Assay for HDAC10 Identifies Selective Inhibitors with Cellular Target Engagement.Chembiochem : a European journal of chemical biology · 2022Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
Histone deacetylases (HDACs) are a family of 18 epigenetic modifiers that fall into 4 classes. Histone deacetylase inhibitors (HDACi) are valid tools to assess HDAC functions. HDAC6 and HDAC10 belong to the class IIb subgroup of the HDAC family. The targets and biological functions of HDAC10 are ill-defined. This lack of knowledge is due to a lack of specific and potent HDAC10 inhibitors with cellular activity. Here, we have synthesized and characterized piperidine-4-acrylhydroxamates as potent and highly selective inhibitors of HDAC10. This was achieved by targeting the acidic gatekeeper residue Glu274 of HDAC10 with a basic piperidine moiety that mimics the interaction of the polyamine substrate of HDAC10. We have confirmed the binding modes of selected inhibitors using X-ray crystallography. Promising candidates were selected based on their specificity by in vitro profiling using recombinant HDACs. The most promising HDAC10 inhibitors 10c and 13b were tested for specificity in acute myeloid leukemia (AML) cells with the FLT3-ITD oncogene. By immunoblot experiments we assessed the hyperacetylation of histones and tubulin-α, which are class I and HDAC6 substrates, respectively. As validated test for HDAC10 inhibition we used flow cytometry assessing autolysosome formation in neuroblastoma and AML cells. We demonstrate that 10c and 13b inhibit HDAC10 with high specificity over HDAC6 and with no significant impact on class I HDACs. The accumulation of autolysosomes is not a consequence of apoptosis and 10c and 13b are not toxic for normal human kidney cells. These data show that 10c and 13b are nanomolar inhibitors of HDAC10 with high specificity. Thus, our new HDAC10 inhibitors are tools to identify the downstream targets and functions of HDAC10 in cells.
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