trichostatin A (VTR-297) / Vanda - LARVOL DELTA

Safety, Tolerability and Efficacy of Trichostatin A in Patients With Mild to Severe Onychomycosis (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Vanda Pharmaceuticals

New P2 trial • Infectious Disease

Causal Inference and Shared Molecular Pathways in Crohn's Disease, Celiac Disease, and Ankylosing Spondylitis: Integrative Mendelian Randomization and Transcriptomic Analysis. (PubMed, Int J Mol Sci) - "Regulatory network and molecular docking analyses further highlighted Trichostatin A as a potential therapeutic agent. These findings reveal shared genetic and immune-related mechanisms, offering novel targets for cross-disease treatment strategies."

Journal • Ankylosing Spondylitis • Celiac Disease • Crohn's disease • Gastroenterology • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Mucositis • Rheumatology • Seronegative Spondyloarthropathies • P2RY8

High-Calorie Diets Exacerbate Lipopolysaccharide-Induced Pneumonia by Promoting Propionate-Mediated Neutrophil Extracellular Traps. (PubMed, Nutrients) - "Propionate supplementation and HDAC inhibitor (trichostatin A) interventions were applied to validate mechanistic pathways...Restoring propionate levels or targeting HDACs may offer therapeutic strategies for diet-aggravated respiratory diseases. Mechanistically, propionate-mediated HDAC inhibition demonstrates proof-of-concept efficacy in modulating H4 acetylation, warranting further investigation in disease-specific pneumonia models."

Journal • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • HDAC1

Epigenetic signatures in in vitro-expanded equine chondrocytes induced by a histone deacetylase inhibitor. (PubMed, Res Vet Sci) - "We have explored the impact of DNA methylation changes on gene transcription in expanded equine chondrocytes treated with the histone deacetylase inhibitor (HDACi), Trichostatin A (TSA)...While TSA was found to hypermethylate and downregulate genes crucial for chondrocyte function, it also hypomethylated and upregulated genes involved in cartilage and bone formation. The findings highlight the TSA's selective activity in modifying epigenetic marks, suggesting its potential as well as limitations in promoting chondrocyte differentiation and regeneration, which is notably relevant for regenerative medicine applications in treating cartilage damage."

Journal • Preclinical

Elucidating the Potential of E-cadherin Re-expression along with Trichostatin A and Zebularine in Enhancing Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis in Human Breast Adenocarcinoma Cells. (PubMed, Curr Cancer Drug Targets) - "In summary, H&E staining showed the positive effect of E-cadherin in sustaining apoptosis induced by TRAIL, especially in combination with TSA and Zeb. However, based on flow cytometry, RT-PCR, and Western blot results, TZ and TRAIL could potentially offer a more effective treatment option for E-MDA-MB-231. These findings suggest that TZ induced intrinsic apoptotic pathway via epigenetic modulation of CDH1 promoter while TRAIL-induced extrinsic apoptotic pathway via improved TRAIL signaling with E-cadherin re-ex-pression, indicating the potentiality of E-cadherin as a biomarker for TRAIL treatment in TNBC."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • BAX • BCL2 • CDH1

Identify Key Genes and Construct the lncRNA-miRNA-mRNA Regulatory Networks Associated with Glioblastoma by Bioinformatics Analysis. (PubMed, Curr Med Chem) - "Our study identified key genes and related lncRNA-miRNA-mRNA network that contribute to the oncogenesis of glioblastoma."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • KCNQ1OT1 • MIR106A • MIR27A

HDAC inhibitors repress Tek and Angpt1 expression and proliferation in RUNX1-MECOM-type leukemia cells. (PubMed, Leuk Res) - "Interestingly, the expression of Tek and Angpt1 was downregulated by HDAC inhibitors (HDACi), trichostatin A (TSA) and valproic acid (VPA)...Furthermore, intraperitoneal injection with VPA, but not TSA, extended the survival of the secondary transplanted mice. These data demonstrate the potential of HDACi as a promising targeted treatment for RUNX1-MECOM-type leukemia."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • ANGPT1 • MECOM • RUNX1 • TEK

Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem Cells. (PubMed, Epigenomes) - "These findings demonstrate that H3K9ac-mediated epigenetic remodeling plays a critical role in the adipogenic differentiation of PDLSCs and identifies TSA as a potential tool for modulating this process."

Journal • PPARG

Restoring impaired osteogenic differentiation of diabetic rat stromal cells using epigenetic inhibitors. (PubMed, Adv Med Sci) - "Our results revealed the underlying epigenetic mechanisms responsible for the impaired osteogenic differentiation capacity of stem cells in diabetes. These findings highlight the potential of epigenetic modulators to restore stem cell function and enhance bone regeneration. This approach holds promise for improving diabetes-related skeletal complications and advancing tissue engineering strategies, including the development of scaffold-based therapies for fracture repair, periodontal regeneration, and implant integration in diabetic patients."

Journal • Preclinical • Diabetes • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • CTNNB1 • RUNX2

SOAR elucidates biological insights and empowers drug discovery through spatial transcriptomics. (PubMed, Sci Adv) - "SOAR's integrative approach toward drug discovery revealed sirolimus and trichostatin A as potential anticancer agents targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin growth and proliferation pathway and identified Janus kinase/signal transducers and activators of transcription inhibitors for ulcerative colitis treatment. SOAR's results demonstrate its broad application to data generated from diverse spatial technologies and pathological conditions. SOAR will support future benchmarking studies and method development, facilitating discoveries in molecular functions, disease mechanisms, and potential therapeutic targets."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CXCL16 • mTOR • SPP1

Harnessing traditional medicine and biomarker-driven approaches to counteract Trichostatin A-induced esophageal cancer progression. (PubMed, World J Gastroenterol) - "Integrating traditional medicine-based interventions with biomarker-driven targeted therapy may enhance ESCC treatment efficacy while minimizing HDACi-associated risks. We advocate for future research focusing on the interplay between epigenetic modulation, natural compounds, and biomarker identification to refine personalized therapeutic strategies for ESCC."

Biomarker • Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • BRD4 • MYC

Epigenetic Histone Deacetylases Activity Assay in the Brain and Peripheral Organ Tissues. (PubMed, Curr Protoc) - "Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolation of nuclear protein from brain and other tissues Support Protocol 1: Harvesting and microdissection of brain and other tissues Support Protocol 2: Estimation of extracted protein using the Pierce bicinchoninic acid (BCA) assay Basic Protocol 2: HDAC activity fluorometric assay in the brain and other tissues."

Journal • CNS Disorders • Oncology • Vascular Neurology

"Epigenetic and Metabolic Regulation: The Role of HDAC2 in Drug Resistance in Steroid Resistant Nephrotic syndrome" (ERA 2025) - "PBMCs were treated with 1µM of Theophylline (HDAC2 stimulator) and 0.8µM of Trichostatin A (HDAC2 inhibitor) for a period of 48 hours... Targeting these pathways could improve treatment outcomes by sensitizing resistant cells to existing therapies, thereby enhancing their efficacy and reducing the likelihood of relapse. Further research is warranted to elucidate the precise mechanisms and therapeutic potential of modulating HDAC2 in drug-resistant diseases."

Glomerulonephritis • Nephrology • Renal Disease • GAPDH • HDAC2

HIV-1 Amplifies IL-8 Response Of Human Stellate Cells To Gram-Positive Microbial Products Via H4K5 Histone Acetylation. (PubMed, bioRxiv) - "Consistent with this, treatment with Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, further increased the IL-8 response in HIV-1-infected HSCs...HIV-1 infection sensitizes HSCs to LTA stimulation, leading to an amplified IL-8 response mediated through histone acetylation that may accelerate liver fibrosis progression in PLWH. As microbial translocation persists despite effective antiretroviral therapy, these findings underscore the need for targeted strategies to mitigate liver fibrosis in HIV-1 infected HIV-1 + individuals."

Journal • Fibrosis • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • COL1A1 • CXCL8

Simulated Microgravity-Induced Alterations in PDAC Cells: A Potential Role for Trichostatin A in Restoring Cellular Phenotype. (PubMed, Int J Mol Sci) - "Trichostatin A (TSA), a histone deacetylase inhibitor, has been recognized as an effective therapeutic agent against PDAC by inhibiting proliferation, inducing apoptosis, and sensitizing PDAC cells to chemotherapeutic agents such as gemcitabine. TSA treatment promotes the downregulation of some markers involved in the maintenance of the potency of stem cells, while it upregulates proteins involved in the induction and modulation of the differentiation process. Our data suggest that TSA treatment restores the cell phenotype prior to simulated microgravity exposure, and exerts an intriguing activity on PDAC cells by reducing proliferation and inducing cell death via multiple pathways."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CDC42

Self-Promoting Targeted Delivery of Epigenetic Immunostimulants to Activate Breast Cancer Immunity via HDACs Downregulation and PD-L1 Upregulation. (PubMed, Angew Chem Int Ed Engl) - "Moreover, Trichostatin A (TSA) is confirmed to suppress HDACs and increase PD-L1 expression...Immunological results confirm robust immunomodulatory effects of SPT-IS, significantly enhancing tumor-infiltrating lymphocytes recruitment and proliferation, leading to notable anti-tumor efficacy. These findings highlight the potential of a self-promoting targeted strategy to enhance drug delivery and provide an epigenetic approach to boost the immune response against breast cancer."

IO biomarker • Journal • Breast Cancer • Immunology • Oncology • Solid Tumor • PD-L1

[Retracted] Breast cancer cells are arrested at different phases of the cell cycle following the re‑expression of ARHI. (PubMed, Oncol Rep) - "The Editor apologizes for any inconvenience caused. [Oncology Reports 31: 2358‑2364, 2014; DOI: 10.3892/or.2014.3107]."

Journal • Breast Cancer • Oncology • Solid Tumor • CCND1 • CDKN1A

Exploring the potential of Gonolobus condurango as a histone deacetylase inhibitor in triple-negative breast cancer cell lines: in vitro study. (PubMed, BMC Complement Med Ther) - "Several classes of HDAC inhibitors have been shown to be potent and specific anticancer agents. In this study, Gonolobus condurango showed no HDAC inhibitory effect in the TNBC cell lines. Identifying new HDAC inhibitors is important, but they must be well characterized before being used as therapeutic agents in humans."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3 • CASP7 • HDAC1 • HDAC2 • HDAC3 • HDAC4 • MIR192 • MIR194

Effects of Integrin-Linked Kinase Silencing Combined With Trichostatin A on Cancer Stem Cells. (PubMed, Oral Dis) - "The study confirms the efficacy of targeting CSCs with ILK silencing and TSA treatment in OSCC, suggesting a promising strategy for CSC-directed therapies that merit further investigation."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Prevention of type 1 diabetes by epigenetic modulation involves restoration of T-cell tolerance and gene regulation without involving the microbiome (IMMUNOLOGY 2025) - "To this end, female NOD mice that develop T1D spontaneously, like humans, were treated with the potent histone deacetylase inhibitor Trichostatin A (TSA)...Thus, the epigenetic drug selectively impacts the immune system, halting the progression of autoimmune diabetes without the profound influence on the gut microbiome. These findings have significant implications for designing novel treatment modalities to impede the progression of autoimmune processes in T1D patients.Keywords: Cells Monocytes/Macrophages Th1/Th2 Cells; Diseases Autoimmunity; Processes Gene Regulation Tolerance/Suppression/Anergy"

Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4

Specific expression and common potential therapeutic drugs in different brain regions of major depressive disorder patients: bioinformatics analysis. (PubMed, J Affect Disord) - "Potential therapeutic drugs included dorsomorphin and trichostatin A. Gene set enrichment analysis (GSEA) revealed significant pathways such as oxidative phosphorylation in the amygdala, TYROBP microglial network in the anterior cingulate cortex, and MAPK signaling pathway in the dorsolateral prefrontal cortex. This study provides a comprehensive bioinformatics analysis of gene expression differences across brain regions in MDD patients. The identified core genes and pathways offer valuable insights into disease mechanisms and potential therapeutic targets, paving the way for future clinical applications."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • COX5A • LMO2 • TYROBP

Development of a BiAD Sensor for Locus-Specific Detection of Cellular Histone Acetylation Dynamics by Fluorescence Microscopy. (PubMed, Genes (Basel)) - "Our data demonstrate that active chromatin modifications can be detected by BiAD sensors using 2xBRD9-BD as a reader. This complements the toolkit of the available BiAD sensors and documents the modularity of BiAD sensors."

Journal

HMGB1 derived from macrophages and enteric glial cells contributes to the butyrate-induced colonic hypersensitivity in mice. (PubMed, Eur J Pharmacol) - "Repeated butyrate treatment caused colonic hypersensitivity to distension and intraluminal sulfide, a functional enhancer of Cav3.2 channels, in mice, which was prevented by repeated treatment with an anti-HMGB1-neutralizing antibody, thrombomodulin alfa (TMα) capable of causing thrombin-dependent degradation of HMGB1, antagonists for RAGE, TLR4 and CXCR4, membrane receptors of HMGB1, liposomal clodronate, a macrophage depletor, and ethyl pyruvate capable of inhibiting HMGB1 release from macrophages...In macrophage-like RAW264.7 cells and EGC-like CRL-2690 cells, butyrate as well as trichostatin A, a well-known HDAC inhibitor, at the same concentrations that increased histone acetylation, evoked cytoplasmic translocation and extracellular release of nuclear HMGB1. Together, butyrate is considered to cause HMGB1 release from macrophages and EGCs most probably by inhibiting HDAC, resulting in colonic hypersensitivity in mice. HMGB1 and its membrane receptors might serve as..."

Journal • Preclinical • Gastrointestinal Disorder • Immunology • Pain • CAV3 • CXCR4 • HMGB1 • S100B • TLR4

Inflammatory cytokines and extracellular matrix remodeling genes are epigenetically regulated in neoplastic HK-2 cells transformed by chronic exposure to arsenic (AACR 2025) - "DNA demethylating agent 5 Aza 2-deoxycytidine and histone deacetylase inhibitor Trichostatin A restored the expression of cytokines and ECM related genes...This suggests aberrant expression of genes is regulated by these histone marks. In summary, the findings of this study suggest epigenetic regulation of inflammatory cytokines and ECM related genes expression by changes in histone marks during arsenic induced neoplastic transformation of HK-2 cells."

Late-breaking abstract • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

NaDC3: a potential tumor suppressor and biomarker in renal cell carcinoma (AACR 2025) - "SDCT2 induction was evaluated following 5-azacytidine plus Trichostatin A treatment. NaDC3 was 63- and 100-fold downregulated in low- and high-stage RCC tissues respectively. This is the first study on a functional biomarker in RCC, NaDC3, that is a possible novel tumor suppressor gene. NaDC3 loss promotes RCC growth and survival and inhibits cellular senescence, while its downregulation correlates with metastasis and racial disparity.Support: 1R01CA227277-05A1; 1R01CA283699-01"

Biomarker • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CASP3 • CDKN2A