Zolinza (vorinostat)

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Mechanistically, HIT211504993 inhibits Myc-driven tumorigenesis by promoting nucleocytoplasmic acetylation and modulating p53, cell-cycle, and Wnt/β-catenin signaling. The investigation of antitumor activity and its mechanism of action provides a theoretical basis for the development of the next-generation benzenesulfonanilide HDAC inhibitors.

P2, N=15, Recruiting, Fred Hutchinson Cancer Center | Trial primary completion date: Jul 2026 --> Dec 2026

Combination strategies, such as vorinostat with ponatinib, provide complementary therapeutic avenues...Hybrid molecules derived from approved TKIs, including GNF-7, olverembatinib, and HG-7-85-01, exemplify rational design trends that balance efficacy with improved safety. Molecular modeling continues to deepen understanding of ligand engagement within the T315I-mutated active site, supporting the development of next-generation inhibitors. In this review, we summarized recent progress in the design, optimization, and biological evaluation of small molecules targeting the BCR-ABLT315I mutation.

SAHA imposes a common anti-proliferative core but engages distinct lineage-conditioned risk modules in LUAD and LUSC-cell-cycle/migration-linked in LUAD and checkpoint/stress-linked in LUSC. These SAHA feature-sensing modules provide a mechanistic and clinically anchored framework for subtype-tailored HDAC-directed combinations and for future development of HDACi-aligned biomarkers in NSCLC.

P1/2, N=43, Active, not recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Oct 2026 --> Apr 2026 | Trial primary completion date: Oct 2025 --> Jul 2025

He was treated with nine cycles of VDC-IE(vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) chemotherapy given at 3-week intervals, complicated by transient iron deficiency anaemia, followed by surgical excision with neck dissection and fibular flap reconstruction. Maintenance therapy with the histone deacetylase inhibitor vorinostat was initiated. This case highlights the importance of early recognition, multimodal therapy and emerging targeted treatment in improving outcomes for NUT carcinoma.

This study establishes ZPLD1 as a prognostic indicator and potential therapeutic target in BLCA, paving the way for precision oncology strategies integrating ZPLD1-guided patient selection and immune-drug combinations.

P2, N=15, Recruiting, Fred Hutchinson Cancer Center | Trial primary completion date: Dec 2025 --> Jul 2026

This study investigates the mechanisms by which histone deacetylase (HDAC) inhibitors induce epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC), focusing on the role of Cathepsin B. Lung cancer cell lines A549 and H1975 were treated with HDAC inhibitors SAHA and SB939, and various assays were conducted to assess cell viability, apoptosis, migration, invasion, and cytoskeletal changes...Cathepsin B was identified as a key mediator of the HDAC inhibitor-induced EMT, which it promotes by interacting with and upregulating the transcription factor Slug. These findings suggest that Cathepsin B is a crucial factor in HDAC inhibitor-induced EMT in NSCLC, indicating that targeting this enzyme may provide a novel therapeutic strategy to counteract invasiveness in lung cancer.

The representative compound 6s demonstrates superior dual-targeting properties, exhibiting 150-fold higher FLT3 inhibition (half-maximal inhibitory concentration (IC50) = 14 nM) compared with the reference drug tandutinib (IC50 = 2098 nM) and 2.9-fold higher HDAC1 inhibition (IC50 = 27 nM) relative to vorinostat (SAHA; IC50 = 79 nM). Importantly, in the Jeko-1 xenograft model, 6s achieves 53.34 % tumor growth inhibition at a dose of 30 mg/kg with no observable toxicity. Collectively, these results indicate that 6s is a potent dual FLT3/HDAC inhibitor with promising therapeutic potential for hematologic malignancies.

This study evaluated daidzein's anti-leukaemic potential using integrated computational, in vitro, and in vivo approaches. Molecular docking and dynamics simulations confirmed stable HDAC7 binding with a binding affinity of -7.6 kcalmol⁻¹, comparable to vorinostat (SAHA; -6.7 kcalmol⁻¹)...HDAC7 suppression was further verified by immunohistochemistry in spleen and liver tissues. Moreover, peripheral blood mononuclear cell profiling showed enhancement of T cells and myeloid cells with concurrent reductions in B cells and macrophages, suggesting immunomodulatory potential.The demonstrated anti-leukaemic and immunomodulatory effects support further investigation toward potential clinical use.