ArticleMolecular medicine (Cambridge, Mass.)
The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects islet β cells in vivo and in vitro.
Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells.Frontiers in cell and developmental biology · 2020Pooled it
- Structure-guided identification of histone deacetylase 11 inhibitors for targeted chemotherapy through long-timescale molecular dynamics simulation.Journal of molecular modeling · 2026Article
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- An Update Comprehensive Review on Epigenetic Modifications and Therapies in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2026Review
- The Diverse Effect of HDAC Inhibitors: Sodium Butyrate and Givinostat on Microglia Polarization After Hypoxia-Ischemia In Vitro.International journal of molecular sciences · 2026Article
- Innovative Therapeutic Approaches Targeting Obesity: Can Flavonoids Improve the Efficacy of Anti-Obesogenic Drugs?International journal of molecular sciences · 2025Review
- Pharmaco-Epigenetics and Epigenetic Drugs in Type 2 Diabetes: Can Epigenetics Predict Drug Efficiency?Biomedicines · 2025Review
- Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.Clinical epigenetics · 2024Review
- ITF2357 regulates NF-κB signaling pathway to protect barrier integrity in retinal pigment epithelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study.Signal transduction and targeted therapy · 2023Review
- Article
- Epigenetic Reprogramming of the Inflammatory Response in Obesity and Type 2 Diabetes.Biomolecules · 2022Review
- An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions.International journal of molecular sciences · 2022Review
- Review
- Protein acetylation derepresses Serotonin Synthesis to potentiate Pancreatic Beta-Cell Function through HDAC1-PKA-Tph1 signaling.Theranostics · 2020Article
- Targeting Type 1 Diabetes: Selective Approaches for New Therapies.Biochemistry · 2019Review
- The discovery of novel HDAC3 inhibitors via virtual screening and in vitro bioassay.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- CKD-506, a novel HDAC6-selective inhibitor, improves renal outcomes and survival in a mouse model of systemic lupus erythematosus.Scientific reports · 2018Article
- Epigenetics of Subcellular Structure Functioning in the Origin of Risk or Resilience to Comorbidity of Neuropsychiatric and Cardiometabolic Disorders.International journal of molecular sciences · 2018Review
- Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
In type 1 diabetes, inflammatory and immunocompetent cells enter the islet and produce proinflammatory cytokines such as interleukin-1β (IL-1β), IL-12, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ); each contribute to β-cell destruction, mediated in part by nitric oxide. Inhibitors of histone deacetylases (HDAC) are used commonly in humans but also possess antiinflammatory and cytokine-suppressing properties. Here we show that oral administration of the HDAC inhibitor ITF2357 to mice normalized streptozotocin (STZ)-induced hyperglycemia at the clinically relevant doses of 1.25-2.5 mg/kg. Serum nitrite levels returned to nondiabetic values, islet function improved and glucose clearance increased from 14% (STZ) to 50% (STZ + ITF2357). In vitro, at 25 and 250 nmol/L, ITF2357 increased islet cell viability, enhanced insulin secretion, inhibited MIP-1α and MIP-2 release, reduced nitric oxide production and decreased apoptosis rates from 14.3% (vehicle) to 2.6% (ITF2357). Inducible nitric oxide synthase (iNOS) levels decreased in association with reduced islet-derived nitrite levels. In peritoneal macrophages and splenocytes, ITF2357 inhibited the production of nitrite, as well as that of TNFα and IFNγ at an IC(50) of 25-50 nmol/L. In the insulin-producing INS cells challenged with the combination of IL-1β plus IFNγ, apoptosis was reduced by 50% (P < 0.01). Thus at clinically relevant doses, the orally active HDAC inhibitor ITF2357 favors β-cell survival during inflammatory conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.