trichostatin A (VTR-297)

Representative compounds, including sulforaphane, erucin, puerarin, capsaicin, curcumin, trichostatin A, trichostatin C, and pinocembrin, highlight the potential of natural products to suppress tumor growth, promote apoptosis, impair migration, and enhance antitumor immunity through acetylation-related mechanisms...These findings support an evidence-oriented translational framework that prioritizes natural products according to mechanistic robustness, bladder cancer specificity, and combination potential. Overall, acetylation-targeting natural products represent a promising but still evolving therapeutic strategy for bladder cancer, warranting further subtype-specific, mechanistically rigorous, and translationally oriented investigation.

Compounds 8o and 8p were identified as potent panHDAC inhibitors. They demonstrated cytotoxicity against triple-negative breast cancer cells. This provides a promising foundation for future structural optimization and preclinical development.

To evaluate the role of protein deacetylases, TPM effects were further analysed in the presence of the deacetylase inhibitors trichostatin A (TSA) and inauhzin. These findings reveal a previously uninvestigated modulatory effect of TPM on cholinergic calcium signalling that is directly dependent on the activity of deacetylases, like Sirt-1. The results may contribute to a better understanding of TPM's anticonvulsive mechanisms of action.

P1, N=42, Recruiting, Vanda Pharmaceuticals | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

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.

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.

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.

P2, N=50, Active, not recruiting, Vanda Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: May 2026 --> Sep 2026 | Trial primary completion date: Mar 2026 --> Sep 2026

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.

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.

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.

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.