Zolinza (vorinostat) / Merck (MSD) - LARVOL DELTA

Characterization of novel anoikis-related genes as prognostic biomarkers and key determinants of the immune microenvironment in esophageal cancer. (PubMed, Front Immunol) - "Furthermore, six potential therapeutic agents for EC were identified: BIRB.0796, Camptothecin, CHIR.99021, Methotrexate, PF.4708671, and Vorinostat. Furthermore, several potential therapeutic agents for EC were identified, offering promising avenues for treatment. These findings hold significant potential for enhancing the survival outcomes of EC patients and provide meaningful guidance for clinical decision-making in managing this malignancy."

Biomarker • Journal • Esophageal Cancer • Oncology • CD40 • CD40LG • CD70 • CDK1 • FOXC2 • HHLA2 • IL17A • MAPK1 • PIP5K1C • TNFRSF14 • TNFRSF25 • TNFSF15 • TNFSF18 • TNFSF8

Molecular biomarker analysis in the phase II basket PEVOSq trial testing pembrolizumab with vorinostat on late-stage squamous cell carcinoma supports HDAC inhibition as an immunotherapy enhancer (ESMO 2025) - No abstract available

Biomarker • IO biomarker • P2 data • Oncology • Squamous Cell Carcinoma

Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial (Nature) - "P2 | N=112 | PEVOsq (NCT04357873) | In the efficacy population (n = 107), the ORR was met in cervical (39%), anal (31%) and vulvar/vaginal (19%) cancer cohorts, but not in head and neck SCC (19%) or penile (18%) cancer cohorts (overall ORR = 26%). Median progression-free survival was 4.0 months (95% confidence interval: 2.6–4.3), and median overall survival was 11.1 months (95% confidence interval: 9.2–17.4). In the safety population, 101 (91%) of 111 patients developed at least one treatment-related adverse event, with 39% and 5.4% of patients experiencing at least one grade 3 and grade 4 treatment-related adverse event, respectively."

P2 data • Cervical Cancer • Lung Cancer • Penile Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Vulvar Cancer

The Construction of ceRNA Regulatory Network Unraveled Prognostic Biomarkers and Repositioned Drug Candidates for the Management of Pancreatic Ductal Adenocarcinoma. (PubMed, Curr Issues Mol Biol) - "In addition to providing novel biomarkers for diagnosis that can be detected non-invasively, the secretion levels of hub genes-associated proteins were found in plasma, serum, and oral epithelium. The drug repositioning analysis revealed vorinostat, meclocycline sulfosalicylate, and trichostatin A, which exhibited significant binding affinities to the hub genes compared to their inhibitors via molecular docking analysis."

Biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • ADAM12 • ZEB2

An Open-Label, Proof of Consent Study of Vorinostat for the Treatment of Mdoerate-to-Severe Crohn s Disease and Maintenance Therapy With Ustekinumab (clinicaltrials.gov) - P1/2 | N=35 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial primary completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

In vitro and in vivo evaluation of 1,4-bis-benzylpiperazine-2-carboxylic acid derivatives as potential multi-target directed ligands (MTDLs) anti-Alzheimer's agents. (PubMed, Bioorg Chem) - "Recently, we reported a series of donepezil-based piperazine-2-carboxylic acid derivatives, essentially designed as MTDLs anti- Alzheimer's agents, with nanomolar to sub micromolar dual inhibitory activity against acetylcholinesterase and butyrylcholinesterase...Meanwhile, compounds 7b, 7e and 8f exhibited comparable in vitro inhibitory activity against HDAC1, (IC50 = 0.30 ± 0.01, 0.14 ± 0.01 and 0.15 ± 0.01 μM respectively), relative to the reference drugs SAHA (IC50 = 0.046 ± 0.002 μM) and entinostat, (IC50 = 0.05 ± 0.002 μM)...Docking studies, in the binding sites of Aβ(1-42) peptide (PDB code 1IYT) and HDAC1 (PDB code 4BKX), demonstrate binding modes analogous to that elicited by the native ligands, respectively. These findings confirm of the neuroprotective activity of the designed compounds and establish their validity as MTDLs candidates for..."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • HDAC1

Hispidulin: a potential alternative to vorinostat against HDAC1 for acute myeloid leukemia. (PubMed, Discov Oncol) - "These findings suggest that hispidulin exhibits superior binding stability and interaction strength with HDAC1 relative to vorinostat. Thus, hispidulin may serve as a promising lead compound for HDAC1 modulation, potentially enhancing therapeutic efficacy in the treatment of acute myeloid leukemia (AML)."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HDAC1

Novel quinazoline-triazole-based N-hydroxybenzamides/N-hydroxypropenamides as HDAC inhibitors: design, synthesis, biological evaluation, and docking studies. (PubMed, RSC Adv) - "Notably, 7d and 11d induced G2/M phase arrest and apoptosis, demonstrating their potential as HDAC inhibitors with promising anticancer properties. Finally, molecular docking studies on HDAC isoforms for the 7a-i and 11a-i series revealed key structural features crucial for the activity of the library compounds."

Journal • Oncology

Dual Targeting using SAHA and Diethyldithiocarbamate (DDC)-Metal Complexes Augments Sodium Iodide Symporter Function in Thyroid and Breast Cancer (ATA 2025) - No abstract available

Breast Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Development of Isoform-Specific HDAC Degraders as a Novel Treatment Option for Corticotroph Tumors (ENDO 2025) - "To determine the optimal HDACi to use in our PROTAC design, we first compared the antiproliferative effects of 11 HDAC inhibitors, 4 of which are FDA-approved, namely vorinostat, romidepsin, belinostat, and panobinostat using human and murine corticotroph tumor (AtT20) cells. This ensures the HDAC PROTAC is only activated in relatively hypoxic conditions, such as that present in corticotroph pituitary tumors and will limit potential adverse effects of the molecule. In summary, we have designed and synthesized a hypoxia-activated HDAC isoform-specific PROTAC; we are optimistic about developing novel, safe, efficacious targeted therapy for patients with Cushing Disease."

Cushing’s Disease • Endocrine Cancer • Oncology • Pituitary Gland Carcinoma • Targeted Protein Degradation • HDAC1 • HDAC2 • HDAC3

In Silico modeling for assessment of the most effective ratio and interaction of anticancer drugs. (PubMed, Biochem Biophys Res Commun) - "In this study, we applied two established mathematical models to assess synergism and optimize the ratio of vorinostat (SAHA) and doxorubicin (DOX) in vitro for breast cancer (BC) models. This combination showed strong efficacy in both 2D and 3D cancer models. Our results highlight the potential value of synergy-based computational tools to guide effective combination therapies in BC and justify further preclinical and in vivo validation of the SAHA/DOX combination."

Journal • Breast Cancer • Oncology • Solid Tumor

Targeting neuroblastoma with hydroxamic acid based HDAC1 and HDAC2 inhibitors: Insights from in vitro and in vivo studies. (PubMed, Invest New Drugs) - "Our findings demonstrated that the newly developed hydroxamic acid analogues, 3A and 3B, effectively inhibited neuroblastoma cells (SH-SY5Y) proliferation, with IC50 values of 8.49 µM and 4.44 µM, respectively, comparable to suberoylanilide hydroxamic acid (SAHA) with IC50 of 0.91 µM...Compound 3B triggered cell cycle arrest in the G2/M phase, reduced colony formation efficiency, and altered cellular architecture upon treatment, further highlighting its anticancer potential. In an in vivo xenograft model, compound 3B significantly decreased tumor growth and tumor weight, highlighting its potential as an effective anticancer agent for neuroblastoma, offering both isoform-selective HDAC inhibition and potent anticancer effects."

Journal • Preclinical • Neuroblastoma • Oncology • Solid Tumor • HDAC2

Deciphering direct transcriptional effects of epigenetic compounds through large-scale new RNA profiling. (PubMed, Nat Commun) - "Notably, chemically similar HDAC inhibitors elicited concordant direct responses and intronic expression analyses mirrored the direct effects seen in new RNA. This work highlights powerful approaches for investigating transcriptional mechanisms."

Journal

AI-assisted Drug Re-purposing for Human Liver Fibrosis. (PubMed, bioRxiv) - "One AI co-scientist recommended drug is an FDA-approved anti-cancer treatment (Vorinostat) that reduced TGFβ-induced chromatin structural changes by 91% and promoted liver parenchymal cell regeneration in microHOs. Hence, the use of AI co-scientist and this microHO platform identified a potential new generation of liver fibrosis treatments that also promote liver regeneration."

Journal • Fibrosis • Immunology • Liver Cirrhosis • Oncology • TGFB1

Martinostat as a novel HDAC inhibitor to overcome tyrosine kinase inhibitor resistance in chronic myeloid leukemia. (PubMed, Clin Epigenetics) - "These findings highlight the potential of martinostat as a selective, low-toxicity HDACi that, combined with TKIs, could provide an effective strategy to overcome drug resistance in CML and improve therapeutic outcomes."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

People living with HIV and TB has a reduced reactivation potential and an increase T cell exhaustion (IAS-HIV 2025) - "Of the 37 people with LTBI, T cell activation and exhaustion markers were assessed in 15 using flow cytometry, and respon3ses to LRAs in 10 (Vorinostat and MC1568) were measured ex vivo using RT-qPCR. Our results indicate that activation markers, such as CD69, CD25, HLA-DR, and CD38 are highly expressed in T cells isolated from people living HIV but not the HIV-TB persons... This suggests that there is stronger immune activation in the HIV-TB people resulting in T cell exhaustion which may impact response to latency reversing agents and reservoir size. It implies that alternative cure methods, or at least more aggressive latency reversal agents, will be necessary for these group of people (HIV-TB individuals). Additional research on reservoir size is ongoing, with results to be presented at IAS 2025."

IO biomarker • Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases • Tuberculosis • CD38 • CD69 • CD8 • IL2RA • ISG20 • LAG3 • PD-1

HDAC Inhibitor Vorinostat in Resistant BRAF V600 Mutated Advanced Melanoma (clinicaltrials.gov) - P1/2 | N=33 | Completed | Sponsor: The Netherlands Cancer Institute | Unknown status ➔ Completed | N=22 ➔ 33

Enrollment change • Trial completion • Melanoma • Oncology • Skin Cancer • Solid Tumor

Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell Lines. (PubMed, Adv Pharm Bull) - "In vitro cytotoxicity study also revealed that VOR loaded FA- PEG-bilosomes demonstrated a greater cytotoxic effect, as compared to the free VOR and VOR- bilosomes in both MCF-7 and 4T1 cancer cells. This showed that FA- PEG-bilosomes could be a promising formulation for the treatment of FA (+) tumors."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

Colon cancer cells evade drug action by enhancing drug metabolism. (PubMed, Oncogene) - "Finally, we identify two clinically accessible approaches to inhibiting drug glucuronidation: (i) blocking an initial HDAC1-mediated deacetylation step of trametinib with the FDA-approved drug vorinostat; (ii) reducing blood glucose by the alpha-glucosidase inhibitor acarbose. Overall, our observations demonstrate a key mechanism by which oncogenic RAS/WNT activity promotes increased drug clearance in CRC and provides a practical path towards abrogating drug resistance in CRC tumours."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • HDAC1 • KRAS • TP53

Epigenetic targeting of DNA damage response (DDR)-related mechanisms to overcome acquired cisplatin resistance of tumor cells. (PubMed, Biochim Biophys Acta Mol Cell Res) - "We investigated the impact of various classes of histone deacetylase inhibitors (HDACi) (i.e. broad-spectrum HDACi (vorinostat), class I HDACi (entinostat), preferential class IIb HDAC6i (ricolinostat) and dual HDAC class I/IIb inhibitors (HDAC1/6i)) on mechanisms of the DDR using parental (J82WT) and cisplatin (CisPt)-resistant bladder carcinoma cells (J82CisR). This is due to amplification of replicative and transcriptional stress caused by CisPt treatment as well as interference with DDR mechanisms and DNA repair, eventually promoting apoptosis. Thus, epigenetic targeting of DDR-related death pathways by class I HDACi is useful to overcome acquired CisPt resistance of tumor cells."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CASP7 • HDAC3 • PARP1

The Spatial Atlas of Human Anatomy (SAHA): A Multimodal Subcellular-Resolution Reference Across Human Organs. (PubMed, bioRxiv) - "All data are openly accessible through a FAIR-compliant interactive portal to support exploration, benchmarking, and machine learning model training. Through SAHA, we provide a foundational framework for spatial diagnostics and next-generation precision medicine grounded in a comprehensive human tissue atlas."

Journal • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Solid Tumor

Epigenetic profiling identifies markers of endocrine resistance and therapeutic options for metastatic castration-resistant prostate cancer. (PubMed, Cell Rep Med) - "Androgen receptor (AR) signaling inhibitors, including enzalutamide, are treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), but resistance inevitably develops...Critically, we identify the pan-HDAC inhibitor vorinostat to be effective in decreasing tumor cell proliferation, both in vitro and in vivo. Moreover, we uncover evidence for HDAC3 working together with glucocorticoid receptor (GR) as a potential mechanism for this therapeutic effect. These findings demonstrate the rationale for therapeutic strategies including HDAC inhibitors to improve patient outcome in advanced stages of mCRPC."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HDAC3

AI-enabled drug prediction and gene network analysis reveal therapeutic use of vorinostat for Rett Syndrome in preclinical models. (PubMed, Commun Med (Lond)) - "Although vorinostat is an inhibitor of histone deacetylases (HDAC), it unexpectedly reverses the Rett phenotype by restoring protein acetylation across hypo- and hyperacetylated tissues, suggesting its activity is based on a previously unknown therapeutic mechanism."

Journal • Preclinical • Developmental Disorders • Genetic Disorders • Movement Disorders • Psychiatry

Low-dose dietary vorinostat increases brain histone acetylation levels and reduces oxidative stress in an Alzheimer's disease mouse model. (PubMed, J Alzheimers Dis) - "This study improves existing preclinical experimental designs by enabling noninvasive manipulation of histone acetylation through dietary intervention. This route of administration provides advantages for future preclinical animal studies."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations. (PubMed, Clin Exp Med) - "The emergence of epigenetic therapies, such as DNA methyltransferase inhibitors (e.g., azacitidine and decitabine), histone deacetylase inhibitors (e.g., vorinostat and romidepsin), and enhancer of zeste homologue 2 inhibitors (e.g., tazmetostat), demonstrates the potential to reverse aberrant epigenetic modifications and restoring normal cellular functions. We emphasize that further study is required to improve delivery systems, comprehend resistance mechanisms and develop precision medicine strategies that can tailor therapies to individual patient profiles. By integrating benchside discoveries with clinical applications, this review aims to illuminate the transformative potential of epigenetic therapies in improving patient outcomes in hematology."

Journal • Review • Acute Myelogenous Leukemia • Gene Therapies • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • EZH2