{
  "id": 3761720,
  "title": "Identification of novel HDAC11 inhibitors: In silico & in vitro studies",
  "url": "https://urgent.news/2026/08/27/identification-of-novel-hdac11-inhibitors-in-silico-in-vitro-studies",
  "topic": "culture",
  "section": "Culture",
  "published": "2026-08-27T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.24.746593v1?rss=1"
  },
  "original_language": "en",
  "account": "Histone deacetylases (HDACs) are vital epigenetic regulators that control a variety of cellular pathways by removing acetyl groups from lysine residues on both histone and non-histone proteins. Among these, histone deacetylase 11 (HDAC11), the unique member of class IV HDACs, possesses both deacetylase and fatty acid deacylase activities. Studies suggest that HDAC11 plays a crucial role in regulating fundamental cellular processes such as metabolism, immune responses, and tissue development. Abnormal HDAC11 activity has been linked to inflammatory diseases, metabolic disorders, neurodegenerative conditions, and cancer, making it a promising therapeutic target. While several HDAC11-selective inhibitors have been identified, none have yet advanced to clinical trials. This study aimed to discover new HDAC11-selective inhibitors by combining computational and experimental methods. Researchers first created a homology model of the HDAC11 structure, which was then validated using structure-based virtual screening, molecular dynamics simulations, and binding free energy calculations. Three lead compounds and their intermediates were identified and validated through biochemical and cell-based assays. The compounds demonstrated potent inhibition of both HDAC11's deacetylase and deacylase activities, with Inhibitor 6 and Inhibitor 3 showing the strongest effects among the six compounds tested. Moreover, inhibition of HDAC11 resulted in decreased lipid accumulation, reduced stability of the HDAC11 substrate SHMT2, as shown by immunoblot analysis, and decreased cell viability in cellular models, as assessed by MTT assay. The findings indicate that these novel HDAC11 inhibitors significantly reduce the viability of breast cancer cells and induce apoptosis, with Inhibitor 6 showing high potency, comparable to the reference compound SIS-17. Flow cytometry confirmed that treated MDA-MB-231 cells exhibited cell-cycle arrest and increased apoptosis, a result corroborated by Annexin V/PI staining. Molecular analysis revealed that BAX increased while BCL2 decreased, suggesting the activation of apoptotic pathways in MDA-MB-231 cells treated with the novel compounds. These results suggest that inhibiting HDAC11 could be an effective strategy to induce cancer cell death, providing a foundation for further evaluation of these compounds as potential treatments for breast cancer. In summary, this study identified promising zinc-chelating HDAC11 inhibitors containing a nitro-sp2 group, which hold significant potential for further therapeutic development.",
  "summary": "Histone deacetylases (HDACs) are pivotal epigenetic regulators that modulate diverse cellular pathways by removing acetyl groups from lysine residues on both histone and non-histone proteins. Histone deacetylase 11 (HDAC11), the sole member of class IV HDACs, exhibits both deacetylation and fatty acid deacylation activities. Accumulating evidence implicates HDAC11 as a key epigenetic regulator of…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}