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

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

Pathogenic variants at the N-terminal arginine residue 44 disrupt human GABA transporter 1 function: insights from Drosophila epilepsy models. (PubMed, Front Pharmacol) - "Proteasome inhibitors (MG-132, bortezomib) and the HDAC inhibitor trichostatin A (TSA) partially rescued R44Q function. Moreover, R44Q-expressing flies presented heat-induced seizures, which were mitigated by 4-phenylbutyrate (4-PBA) treatment. These findings elucidate the molecular basis of R44-mediated hGAT-1 dysfunction and highlight potential therapeutic avenues for SLC6A1-related neurodevelopmental disorders."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Psychiatry

TMOD2 and DOCK4 as Novel Gut Microbiota-Associated Biomarkers for Colorectal Adenoma: Integrated Transcriptomic Analysis and Therapeutic Target Identification. (PubMed, Mediators Inflamm) - "Drug screening identified 22 potential therapeutic compounds, with trichostatin A showing optimal binding affinity. These findings establish TMOD2 and DOCK4 as novel biomarkers linking GM dysbiosis to CRA development, opening new avenues for microbiome-targeted early intervention strategies."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • EIF6

Therapeutic Perspectives of SIRT6 Regulation: Computational Analysis of Activation and Inhibition by Bioactive Molecules. (PubMed, J Mol Recognit) - "Therefore, we investigated the interactions between the ligands quercetin (QUE), isoquercetin (ISO), catechin gallate (CG), and trichostatin A (TSA) with SIRT6, using computational methods from the perspective of molecular modeling through the Molecular Fractionation with Caps Conjugates (MFCC) technique and according to the calculation parameters of Density Functional Theory (DFT)...In addition, residues such as PRO62, MET136, MET157, and VAL115 stand out as key components of the protein active site. These findings offer strategic insights into the molecular mechanisms underlying the binding of the studied ligands to SIRT6, providing a deep understanding of their affinity and pharmacological potential."

Journal • Metabolic Disorders • Oncology • SIRT6

The impact of histone deacetylase inhibition on neurobehavioural outcomes in preclinical models of traumatic and non-traumatic spinal cord injury: a systematic review. (PubMed, Front Immunol) - "Valproate was the most frequently studied HDAC inhibitor (n=20), followed by 4-phenylbutyrate (4-PBA; n=7) and RGFP966 (n=3). Trichostatin A, tubastatin A, entinostat, PCI-34051, scriptaid, CI-994, TMP269, vorinostat, 3-TYP, SW-100 and ACY1215 were each evaluated in a single study. Three studies used the sirtuin-1 (HDAC class III) inhibitor EX527 administered with an activator molecule: melatonin (n=1), MLN4924 (n=1) and oxymatrine (n=1)...These results support further investigation of HDAC inhibitors in preclinical studies before translation into clinical trials. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023477882."

Journal • Preclinical • Review • CNS Disorders • Orthopedics • Pain • Psychiatry • Reperfusion Injury • SIRT1

Selective HDAC4 inhibition by SP1-PTD promotes odontoblast differentiation. (PubMed, J Appl Oral Sci) - "SP1-PTD represents a first-in-class selective HDAC4 inhibitor that achieves robust pro-differentiation effects with an exceptional safety profile. By specifically targeting HDAC4-SMRT interactions, SP1-PTD overcomes limitations of conventional HDAC inhibitors and offers translational promise for dental regenerative medicine."

Journal • BGLAP • DSPP • HDAC4 • RUNX2

Trichostatin A Sensitizes Tumor Cells to Apoptosis Induced by Soluble Trimeric TRAIL-Expressing Human Mesenchymal Stromal Cells. (PubMed, Cancer Sci) - "These in vivo findings indicate that efficient tumor targeting by MSCs is crucial for achieving therapeutic efficacy, especially in TRAIL-resistant tumors. Overall, our results demonstrate that co-treatment with TSA enhances the antitumor effect of TRAIL-expressing MSCs, offering a potential strategy to overcome TRAIL resistance and improve MSC-based cancer therapies."

Journal • Oncology • CASP8

Comparative Study of Histone Deacetylase Inhibitors for Radiation Protection Using Survival Outcomes in a Mouse Model. (PubMed, Biol Pharm Bull) - "Male ICR mice received 7.5 Gy TBI followed by a single administration of valproic acid (VPA; 300 or 600 mg/kg), sodium butyrate (NaB; 500 or 1000 mg/kg), trichostatin A (TSA; 0.5 or 1.0 mg/kg), vorinostat (10 or 50 mg/kg), panobinostat (25 or 50 mg/kg), givinostat (5 or 10 mg/kg), or entinostat (25 or 50 mg/kg). VPA's efficacy may reflect a combination of effects on DNA repair, inflammation, and redox regulation rather than HDAC inhibition alone. These findings suggest VPA to be a promising candidate for radioprotection and emphasize the need for further studies to optimize dosing and explore underlying mechanisms."

Clinical • Journal • Preclinical • Inflammation

Epigenetically inhibiting CYP3A5 modulates the migration and invasion of esophageal squamous cell carcinoma. (PubMed, Drug Metab Dispos) - "Intriguingly, administration of the histone deacetylase inhibitor trichostatin A resulted in the upregulation of CYP3A5 expression...Because ESCC develops, CYP3A5 suppression promotes tumor metastasis and invasion. CYP3A5 is a potential biomarker and therapeutic target for ESCC."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • CREBBP • CYP3A5 • HDAC4

Microhand Platform Equipped with Plate-Shaped End-Effectors Enables Precise Probing of Intracellular Structure Contribution to Whole-Cell Mechanical Properties. (PubMed, Micromachines (Basel)) - "To validate the system's sensitivity, we precisely quantified the mechanical contributions of subcellular components, such as the actin cytoskeleton and chromatin, by measuring stiffness reductions after treatment with Cytochalasin D and Trichostatin A, respectively...Furthermore, by controlling the indentation speed and depth, the mechanical properties of the cytoplasm and nucleus could be distinctly evaluated. These results demonstrate that our microhand system is a highly sensitive and robust platform, capable of detecting subtle, disease-related changes and elucidating the contributions of specific subcellular structures to cell mechanics."

Journal