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

HISTONE DEACETYLASE INHIBITION AMELIORATES RENAL FIBROSIS BY INDUCING DEDIFFERENTIATION AND APOPTOSIS OF MYOFIBROBLASTS (ISN-WCN 2026) - "Given that the transformation of fibroblasts into myofibroblasts in injured kidneys is reversible (Souma et al., J Am Soc Nephrol 2013), this study aimed to identify methods—specifically those that restore fibroblastic properties to myofibroblasts—as therapeutic strategies against renal fibrosis and, eventually, CKD.Methods Because we previously reported that histone deacetylase (HDAC) inhibitors restored EPO-producing capability to neural cells derived from EPO-producing embryonic cells (Iwamura et al., Mol Cell Biol 2025), we investigated the effects of HDAC inhibitors (romidepsin, trichostatin A, and oxamflatin) on the cell fate of two models: Replic cells (a myofibroblast cell line derived from murine renal EPO-producing fibroblasts, Sato et al., Sci Rep 2019) and primary renal myofibroblasts non-invasively obtained from the urine of a patient with CKD. Furthermore, HDAC inhibition restored the EPO-producing capability and fibroblastic signatures (including CD73..."

Epigenetic controller • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • CD73 • HDAC1 • HDAC2 • NT5E

Tolerability Study of Trichostatin A In Subjects With Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Vanda Pharmaceuticals | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Oncology

TSA-ultrasound synergy enhances CRISPR-Cas9 gene editing efficiency in diploid yeast. (PubMed, J Microbiol Methods) - "Key parameters were systematically optimized, and 200 nM Trichostatin A (TSA) (10h) followed by 200 W sonication (3 min) were established as the optimal condition set...Importantly, it enabled complex edits that were previously unattainable in C. glycerinogenes, including the precise deletion of a 7.8-kb fragment and the editing of an 11.4-kb region for functional genomics. In summary, this study establishes a simple and effective workflow that overcomes chromatin-based barriers in the polyploid industrial yeast C. glycerinogenes, providing a practical tool for genetic engineering and functional genomics in this and potentially other recalcitrant yeasts."

Journal

Frizzled-9 Expression Is Associated With Aggressive Clinicopathological Features and Reduced Overall Survival in Invasive Breast Carcinoma. (PubMed, Pathol Int) - "In parallel, breast cancer cell lines were treated with trichostatin A, 5-aza-2'-deoxycytidine, cisplatin, doxorubicin, paclitaxel, and ionizing radiation, followed by quantification of FZD9 mRNA levels by RT-qPCR. Baseline FZD9 transcript levels varied substantially across cell lines, and transcriptional responses to chemotherapy, radiation, and epigenetic treatment were highly context-dependent, with divergent patterns observed according to molecular background. Collectively, these findings indicate that FZD9 expression in breast cancer is heterogeneous, associated with aggressive clinicopathological features, and dynamically modulated by therapeutic exposures, supporting its consideration as an exploratory marker of tumor aggressiveness and therapy-related biological responses."

Biomarker • Journal • Breast Cancer • Gene Therapies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Screening of tyrosine phosphatase SHP2 (PTPN11) inhibitors from natural products with therapeutic potential for receptor tyrosine kinase-driven cancer. (PubMed, J Pharm Anal) - "Trichostatin A (TSA) bound to the "tunnel" binding site, acting as an allosteric inhibitor. This study illustrates an optimized screening methodology and tactics to identify novel SHP2 modulators from NPs and provides a foundation for further NP-based drug development for the treatment of RTK-driven cancer."

Journal • Oncology • PTPN11

An acetylation-dependent switch underlies host disease tolerance during streptococcal infection. (PubMed, Sci Rep) - "Crucially, a focused re-analysis of existing transcriptome datasets from Histone Deacetylase (HDAC)-inhibited macrophages suggested that Trichostatin A (TSA) abrogates the protective transcriptome in ΔPdh infection, indicating that acetylation-dependent repression functions as a key regulator of the host DT response. By integrating new experimental data with advanced computational analyses, our work reveals a bacterial strategy of metabolic-epigenetic crosstalk, suggesting acetylation as a critical control point for mitigating infection-associated tissue damage."

Journal • Infectious Disease • Metabolic Disorders • IL10

The gut microbiota metabolite isovalerate enhances the epithelial barrier function in cell monolayers derived from porcine ileum organoids. (PubMed, Am J Physiol Gastrointest Liver Physiol) - "Furthermore, the structurally unrelated HDAC inhibitor trichostatin A improved epithelial barrier function and upregulated SLPI and IL10RA gene expression, as observed with isovalerate and butyrate...Overall, our in vitro results suggest that targeting the bacterial production of isovalerate may be useful to promote gut health. In this perspective, we performed an in silico analysis that identified species belonging to dominant gut microbiota genera such as Prevotella, Blautia, Christensenella, Clostridium, and Ruminococcus, as potential producers of BCFAs through the POR enzymatic pathway."

Journal • Preclinical

Target epigenetics mechanism to prevent synaptic dysfunction of adult amblyopia. (PubMed, Neurosci Lett) - "First, we established adult amblyopia mice model, which were then randomized into five groups: untreated amblyopia, standard housing, EE, vehicle, trichostatin A (TSA) groups, with normal mice serving as controls...These results indicate that broad HDAC inhibition can mimic EE-induced plasticity in adult amblyopia, while highlighting the need for selective HDAC3-targeted approaches to determine mechanistic specificity. Overall, our study provides a foundation for developing epigenetic-based strategies to enhance adult visual cortical plasticity."

Journal • CNS Disorders • Developmental Disorders • Ophthalmology • Psychiatry • HDAC3

MINFLUX dissects nucleosome and compacting chromatin structures in living cells. (PubMed, Natl Sci Rev) - "Most of the chromatin fibers are dismissed after Trichostatin A (TSA) treatment...Therefore, chromatin fibers (∼30 nm) do exist in living cells, at least in AT-rich regions of the genome. The MINFLUX nanoscopy reveals the native chromatin ultrastructure and its folding to achieve structural compaction in the nucleus."

Journal

KMT2C Loss Promotes NF2-Wildtype Meningioma Progression and Ferroptosis Sensitivity via Epigenetic Repression of Hippo Signaling. (PubMed, Adv Sci (Weinh)) - "Pharmacological restoration of histone acetylation with the HDAC inhibitor Trichostatin A (TSA) effectively suppressed tumor growth. Collectively, our findings identify KMT2C as a key epigenetic regulator linking promoter histone acetylation, NF2-Hippo pathway activity, and ferroptosis susceptibility. These results provide mechanistic insights into high-grade meningioma progression and highlight ferroptosis induction and epigenetic modulation as promising therapeutic strategies for NF2-wild-type, KMT2C-deficient meningiomas."

Journal • Brain Cancer • Meningioma • Oncology • Solid Tumor • EP300 • KMT2C

Safety, Tolerability and Efficacy of Trichostatin A in Patients With Mild to Severe Onychomycosis (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Vanda Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: May 2026 ➔ Sep 2026 | Trial primary completion date: Mar 2026 ➔ Sep 2026

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease

Therapeutic Effects of HDAC Inhibitors on the Progression of Hereditary Hearing Loss (ARO 2026) - "In the second model, Alport syndrome (AS) mice harboring type IV collagen mutations affecting the cochlear basement membrane received trichostatin A (TSA, 10 mg/kg/day) from 3 to 7 weeks of age... These findings suggest that HDAC inhibitors, such as VPA and TSA, hold therapeutic potential to slow the progression of hereditary HL by protecting cochlear structures and modulating oxidative stress and inflammation. This may provide a prolonged therapeutic window for more effective intervention in patients with genetic hearing loss."

Genetic Disorders • Inflammation • Otorhinolaryngology • CDC37 • HDAC1

Comparative multi-omics in female mice reveals tissue-specific vulnerabilities to chronic alcohol intake. (PubMed, Alcohol Clin Exp Res (Hoboken)) - "Overall, this study provides a list of therapeutic targets and treatments to help expedite the understanding of and countermeasures against ALD and myopathy in humans."

Clinical • Journal • Preclinical • Hepatology • Myositis

Single-cell analysis reveals neuroprotective histone deacetylase inhibitor pathways. (PubMed, Alzheimers Dement) - "DISC1 represents a convergent therapeutic target for AD, mediating TSA's neuroprotective effects through pathways regulating GSK3β, mitochondrial transport, and synaptic plasticity, providing a mechanistic framework for developing AD therapeutics."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Psychiatry • Schizophrenia

Nucleosome Clustering as a Biomarker and Mechanistic Switch for Reprogramming Cells. (PubMed, Cells) - "Consistently, pharmacological agents-Trichostatin A as a histone deacetylase inhibitor and chaetocin as a histone methyltransferase inhibitor-induced nucleosome scattering and converted U2OS cells into iTS cells, whose conditioned media exerted tumor-suppressive effects. Our findings highlight nucleosome clustering as a key epigenetic feature responsive to both biophysical and chemical cues, underscoring its role in microscale chromatin remodeling and reprogramming of the tumor microenvironment."

Biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • KDM3A

Trichostatin A Influences Dendritic Cells' Functions by Regulating Glucose and Lipid Metabolism via PKM2. (PubMed, Molecules) - "Mechanistically, PKM2 modulates glucose and lipid metabolism via its dimer formation. These results deepen our understanding of the interplay among TSA, glucose and lipid metabolism and DC functions in MI."

Journal • Cardiovascular • Metabolic Disorders • Myocardial Infarction • PKM

Histone Acetylation Retards the Adipogenic Differentiation of Human Umbilical Cord - Mesenchymal Stem Cells: A Clue for Anti-obesity Approach? (PubMed, Curr Pharm Des) - "Taken together, the results show a possible anti-obesity effect of histone deacetylation inhibitors (HDCAs) in MSCs, resulting in depletion and restriction of their adipogenic differentiation."

Journal • Genetic Disorders • Obesity

In Vitro and In Vivo Antiviral Activity of Histone Deacetylase Inhibitors Against GCRV. (PubMed, J Fish Dis) - "We conducted in vitro and in vivo studies to assess the effects of HDACi on GCRV: trichostatin A (TSA), a traditional HDACi...These findings indicate that HDACi exert a potent antiviral effect against GCRV by modulating host antiviral immune gene expression. Given this host-directed mechanism, it is plausible that HDACi may pose a lower risk of inducing viral resistance compared to direct-acting antivirals, highlighting their potential as candidates for new treatments against grass carp haemorrhagic disease."

Journal • Preclinical • Infectious Disease

Intratumoral Heterogeneity of MAGED4 Expression in Oral Squamous Cell Carcinoma: Epigenetic Mechanisms and Therapeutic Implications. (PubMed, Int J Mol Sci) - "To functionally validate these findings, we treated OSCC cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (DAC) and histone deacetylase inhibitors trichostatin A (TSA) and valproic acid (VPA). The triple-drug combination treatment resulted in the most robust reactivation of MAGED4 expression, correlating with promoter DNA demethylation and enhanced acetylation of H3K9 and H3K27 at the MAGED4 promoter. Our findings elucidate critical epigenetic mechanisms contributing to MAGED4 heterogeneity in OSCC and highlight the potential of combination epigenetic therapies to reverse this heterogeneity, thereby providing a foundation for exploring such approaches to improve immunotherapeutic outcomes."

Heterogeneity • IO biomarker • Journal • Gene Therapies • Melanoma • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • MAGEA4

Development, Live Birth and Fertility in Mouse Oocytes Penetrated by Spermatids Exposed to the HDAC Inhibitor Scriptaid. (PubMed, Reprod Med Biol) - "Additionally, all second-generation offspring were also healthy. Scriptaid improved the developmental potential of ROSI embryos, and no clear teratogenic effect was observed in the live offspring, suggesting that Scriptaid is safer than Trichostatin-A, which has been reported to induce hypomorphic offspring in ROSI."

Journal • Preclinical

Role of Trichostatin A (TSA) in modulating the epigenetic modification in the lymphocytes of colorectal cancer (CRC). (PubMed, Clin Epigenetics) - "Although previous research focuses on the direct impact of TSA on tumor cells, in our study, we exclusively highlight TSA ability to reprogram the immune cells epigenetically in a more inflammatory tumor-reactive phenotype. The findings justify the possibility of TSA as an epigenetic adjunct of low toxicity in immuno-oncology and form a basis to continue in vivo and translational study in CRC immunotherapy."

IO biomarker • Journal • Colorectal Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • FOXP3 • GATA3 • GZMB • HDAC1 • IFNG • IL10 • IL12A • IL17A • IL4 • TBX21 • TNFA • TP53

HDAC6-mediated PFKL deacetylation enhances aerobic glycolysis and promotes VSMC proliferation. (PubMed, J Biol Chem) - "HDAC6, acts as the deacetylase of PFKL, could interact with PFKL to enhance enzymatic activity of PFKL by accelerating PFKL tetrameric formation and aerobic glycolysis process, thereby promoting VSMC proliferation, which can be hindered through the application of HDAC inhibitor Trichostatin A (TSA) or siHDAC6...The recombinant adenoviral vector carrying PFKL K563R mutant aggravated, while the K563Q mutant attenuated PDGF-BB-induced VSMC proliferation and ligation-induced neointimal formation. Thus, PFKL may be a potential target for vascular reconstruction diseases treatment."

Journal • Cardiovascular • PFKL

Isoform-specific vs. pan-histone deacetylase inhibition as approaches for countering glioblastoma: an in vitro study. (PubMed, Front Oncol) - "Our results show that the specific HDAC-6 inhibitor Tubacin had a more potent anti-proliferative effect in both the cytotoxicity and live-dead assays. The non-specific inhibitor Vorinostat surprisingly promoted migration in the cells at its 2D IC50 value treatment, and none of the inhibitors was able to significantly decrease late resistance compared to untreated controls, indicating the need for the development of more potent HDAC inhibitors for monotherapy for GBM."

Journal • Preclinical • Brain Cancer • Gene Therapies • Glioblastoma • Oncology • Solid Tumor

Differential effects of HDAC inhibitors in the RhoI255d mouse model for autosomal dominant retinitis pigmentosa. (PubMed, Cell Death Discov) - "Treatment with the HDAC class I/II inhibitor Trichostatin A and the HDAC class III inhibitor nicotinamide (NAM) suggested that most HDAC activity detected in RhoI255d/+ photoreceptors was related to class I/II isoforms...HDAC inhibitors tested included SAHA (Vorinostat), MPT0G211, ACY-957, and NAM...Our study highlights the complexity and ambiguity of HDAC activity during photoreceptor neurodegeneration and cautions against the use of unspecific inhibitors. At the same time, it showcases important differences between rod and cone photoreceptors and suggests especially HDAC-6 as a potential target for future therapy development."

Journal • Preclinical • CNS Disorders • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CAPN2 • CASP3

Zinc-Dependent Histone Deacetylase (HDAC) Inhibitors: Therapeutic Potential, Pharmacophore Structure, and Methods for Testing Deacylase Activity (PubMed, Mol Biol (Mosk)) - "In 1976, the antifungal hydroxamic antibiotic trichostatin A (TSA) was isolated from the metabolites of the bacterium Streptomyces hygroscopicus...New strategies are needed to overcome these problems, including the development of inhibitors targeting a specific class of HDACs. In addition to the most important characteristics of histone deacetylases and their natural inhibitors, this review considers current approaches to the design of selective HDAC inhibitors and the methods used to test them."

Journal • Review • Oncology