ArticlePharmaceuticals (Basel, Switzerland)2022
Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis.
Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Protein acylation in inflammatory diseases: from mechanisms to therapeutic strategies.Cell communication and signaling : CCS · 2025Review
- Fluorinated Analogs of Organosulfur Compounds from Garlic (Molecules (Basel, Switzerland) · 2025Article
- Arylcarboxamide Derivatives as Promising HDAC8 Inhibitors: An Overview in Light of Structure-activity Relationship and Binding Mode of Interaction Analysis.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Integrative machine learning and multi-omics framework identifies shared biomarkers for rheumatoid arthritis and ulcerative colitis.PloS one · 2025Article
- Histone deacetylase in inflammatory bowel disease: novel insights.Therapeutic advances in gastroenterology · 2025Review
- Histone Deacetylase (HDAC) Inhibitors as a Novel Therapeutic Option Against Fibrotic and Inflammatory Diseases.Biomolecules · 2024Review
- The functional roles of short chain fatty acids as postbiotics in human gut: future perspectives.Food science and biotechnology · 2024Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory bowel diseases (IBD) are digestive tract disorders that involve chronic inflammation with frequent recurrences. This study aimed to evaluate the efficacy of two novel histone deacetylase 8 (HDAC8) inhibitors, namely, SPA3052 and SPA3074, against dextran sulfate sodium (DSS)-induced experimental colitis. Male C57BL/6N mice were subjected to two cycles of 1.5% DSS followed by treatment with suberoylanilide hydroxamic acid (SAHA), SPA3052, or SPA3074 for 14 days. Our results showed that SPA3074 administration increased (>50%) the expression of occludin, a tight junction protein, which was significantly decreased (>100%) after DSS treatment. Moreover, SPA3074 upregulated suppressor of cytokine signaling 1 (SOCS1) protein expression, which is known to be a key suppressor of T-helper cell differentiation and pro-inflammatory cytokines expression. Furthermore, we observed a decrease in SOCS1-associated Akt phosphorylation and an increase in lower extracellular signal-regulated kinase 1 and 2 phosphorylation, which contributed to lower nuclear factor-kappa B activation. Th2 effector cytokines, especially interleukin-13, were also downregulated by SPA3074 treatment. This study suggests that HDAC8 might be a promising novel target for the development of IBD treatments and that the novel HDAC8 inhibitor SPA3074 is a new candidate for IBD therapeutics.
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Registered trials
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