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

ONGOING PHASE 2, OPEN-LABEL, MULTICENTER, SINGLE-ARM STUDY ASSESSING AN EVERY-4-WEEK DOSING SCHEDULE OF MOGAMULIZUMAB IN CUTANEOUS T-CELL LYMPHOMA: PRELIMINARY RESULTS (ICML 2025) - P2 | "In the phase 3 MAVORIC study (N = 372), mogamulizumab, given 1 mg/kg weekly in cycle (C) 1 and then biweekly (Q2W), demonstrated superior efficacy versus vorinostat and a manageable safety profile. Preliminary results showed a promising safety profile and response rates of 2 mg/kg Q4W mogamulizumab."

Clinical • P2 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • CD7 • DPP4

NOVEL CTCL RISK STRATIFIER INTEGRATING LYMPH NODE VOLUMETRICS AND mSWAT TO PREDICT SURVIVAL AND THERAPY RESPONSE (ICML 2025) - " The patient cohort included 262 patients enrolled in the landmark phase 3 clinical trial testing mogamulizumab versus vorinostat in previously treated CTCL (MAVORIC). This study highlights the limitations of current unidimensional lymph node measurements and demonstrates the value of these novel techniques. Volumetric measurements provide a powerful static predictor of survival and kinetic modeling adds a dynamic layer that can guide early treatment decisions and potentially predict lymph node involvement."

Cutaneous T-cell Lymphoma • Lymphoma

Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2. (PubMed, Int J Mol Sci) - "GPB, PA, ursodeoxycholic acid (UDCA), alone or in combination with 4-PB, suberoylanilide hydroxamic acid (SAHA), C18, VX-445, and/or VX-661, significantly corrected both the traffic and the activity of Abcb11R1128C. Such correctors could represent new pharmacological insights for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the transporter's traffic."

Journal • Cholestasis • Hepatology • ABCB1

Dysregulation of Host Histone Acetylation by Acinetobacter baumannii: A Novel Mechanism for Autophagy Inhibition and Bacterial Survival. (PubMed, ACS Infect Dis) - "Since H3K9ac is known to regulate the transcription of autophagy-related genes, we used vorinostat (SAHA), a pan-HDAC inhibitor, to restore H3K9ac levels during A. baumannii infection...Additionally, we observed that SAHA promotes the fusion of autophagosomes and lysosomes mediated by SNARE proteins, enhancing the intracellular clearance of A. baumannii. This study highlights the epigenetic modulations induced by A. baumannii and suggests targeting the host histone acetylation machinery as a potential alternative treatment strategy to combat multidrug-resistant isolates."

Journal • Infectious Disease • ATG16L1 • ATG4C • ATG5 • ATG9B

Sodium Thiosulfate Otoprotection During Salvage Cisplatin Therapy (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati | Trial primary completion date: Jan 2025 ➔ Jan 2027

Trial primary completion date • Embryonal Tumor • Hepatoblastoma • Oncology • Solid Tumor • AFP

Epigenetic Histone Deacetylases Activity Assay in the Brain and Peripheral Organ Tissues. (PubMed, Curr Protoc) - "Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolation of nuclear protein from brain and other tissues Support Protocol 1: Harvesting and microdissection of brain and other tissues Support Protocol 2: Estimation of extracted protein using the Pierce bicinchoninic acid (BCA) assay Basic Protocol 2: HDAC activity fluorometric assay in the brain and other tissues."

Journal • CNS Disorders • Oncology • Vascular Neurology

A screen of chromatin-targeting compounds identifies TAF1 as a novel regulator of HIV latency. (PubMed, bioRxiv) - "BAY-299 reactivated HIV expression and enhanced the efficacy of established latency-reversing agents (LRAs), including vorinostat, prostratin, and iBET-151, in cell line models. These findings highlight a previously unrecognized mechanism of HIV latency control and identify TAF1 as a potential therapeutic target. Understanding how host chromatin regulators contribute to latency is essential for developing strategies that aim to eliminate the persistent HIV reservoir."

Journal • Human Immunodeficiency Virus • Infectious Disease • TAF1

Histone deacetylase inhibitors sensitize glioblastoma models to temozolomide and reprogram immunosuppressive myeloid cells. (PubMed, Res Sq) - "This study evaluated the effects of three HDACis-CAY10603, vorinostat (SAHA), and valproic acid (VPA)-on human GBM cell lines (U87, MGG8) with immortalized human astrocytes (IHAs) as healthy controls. These findings suggest that HDAC inhibition-including the novel small molecule CAY10603-sensitizes GBM to temozolomide and confers potent anti-tumor effects that combat GBM (e.g., reducing proliferation, EMT, stemness). Our in vitro findings -e.g., with 3D neurospheres that better mimic physiological tumor growth than 2D monolayers-warrant future in vivo testing of HDACis alone or in combination with chemotherapy."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CASP3 • TGFB1 • TNFA

VALOR study: A phase II trial of vorinostat to augment response to 177Lutetium-PSMA-617 in the treatment of patients with PSMA-low metastatic castration resistant prostate cancer. (ASCO 2025) - P2 | "Funded by Novartis Clinical Trial Registration Number: NCT06145633 Background: 177Lu-PSMA-617 (LuPSMA), a prostate specific membrane antigen (PSMA) targeting radioligand therapy, is approved for men with mCRPC. These molecular studies will be correlated with the pre/post vorinostat PSMA PET images and clinical outcomes with LuPSMA. Clinical trial information: NCT06145633."

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs • FOLH1

HDAC inhibitors engage MITF and the disease-associated microglia signature to enhance amyloid β uptake. (PubMed, Brain Behav Immun) - "Here, we present a pharmacological approach to mimic human DAM in vitro: we validated in silico predictions that two different histone deacetylase (HDAC) inhibitors, Entinostat and Vorinostat, recapitulate aspects of the DAM signature in two human microglia-like model systems. Further, we functionally characterized our DAM-like model system, showing that the upregulation of this transcriptional program by HDAC inhibitors leads to an upregulation of amyloid β and pHrodo Dextran uptake - while E.coli uptake is reduced - and a specific reduction of MCP1 secretion in response to IFN-γ and TNF-α. Overall, our strategy for compound-driven microglial polarization offers potential for exploring the function of human DAM and for an immunomodulatory strategy around HDAC inhibition."

Journal • CNS Disorders • IFNG • MITF • TNFA

Kirenol alleviates cerebral ischemic injury by promoting synaptic plasticity via HDAC2-mediated BDNF expression. (PubMed, Phytomedicine) - "Kir exerted its protective effects through acetylation changes in histones and increased expression of BDNF-specific isoforms, thereby safeguarding neurons, promoting synaptic plasticity, and offering potential as a therapeutic agent for ischemic stroke."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke • Oncology • Vascular Neurology • BDNF • HDAC2

Production of Aniline Derivatives from Cladosporium cladosporioides TFU-13 and Volutella sp. TFU-28 in the Presence of SAHA. (PubMed, Chem Biodivers) - "Biotransformation of suberoylanilide hydroxamic acid (SAHA) by soil-derived Cladosporium cladosporioides TFU-13 and Volutella sp...Structural elucidation of the novel metabolites was conducted using comprehensive nuclear magnetic resonance (NMR) and high-resolution mass spectrometric analyses. Among these, 2-acetamidophenol (6) displayed antioxidant activity, as indicated by diphenylpicrylhydrazyl (DPPH) radical scavenging assays."

Journal

Rational Design of Novel Quinazolinone-Pyrrolodihydropyrrolone Analogs as PIM/HDAC Dual-Target Inhibitors for the Treatment of Acute Myelocytic Leukemia. (PubMed, J Med Chem) - "Furthermore, 22 demonstrated significant anticancer efficacy (TGI = 81.3%; 50 mg/kg, QD) in the MV4-11 xenograft model without notable toxicity. In conclusion, our study established the therapeutic potential of dual PIM/HDAC inhibitors and provided a tool to elucidate synergistic mechanisms underlying the combined inhibition of these targets."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • PIM1

Vorinostat for Graft-versus-host Disease (GVHD) Prevention in Non-Malignant Adolescent and Young Adults (AYA) Population (clinicaltrials.gov) - P2 | N=55 | Not yet recruiting | Sponsor: Sung Won Choi

New P2 trial • Graft versus Host Disease • Immunology • Transplantation

Revumenib for Relapsed or Refractory Acute Leukemia With a KMT2A Translocation. (PubMed, Ann Pharmacother) - P1/2 | "Revumenib is an innovative targeted treatment with promising activity in r/r acute leukemia with KMT2Ar."

Journal • Review • Acute Myelogenous Leukemia • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pediatrics • Thrombosis • Transplantation • KMT2A

PCB153 induces epileptic-like behaviors in zebrafish by disrupting the GABA pathway. (PubMed, Comp Biochem Physiol C Toxicol Pharmacol) - "In conclusion, PCB153 exposure disrupts the GABAergic neurotransmitter system, which may be a key mechanism underlying the epileptic-like behaviors in zebrafish, and SAHA treatment could potentially have therapeutic effects. This study provides new insights into the toxic effects of environmental pollutants on the nervous system and offers experimental evidence for future neuroprotective strategy research."

Journal • Epilepsy

Vorinostat in Treating Patients With Metastatic Melanoma of the Eye (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Aug 2025 | Trial primary completion date: Dec 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Predicting gene expression changes upon epigenomic drug treatment. (PubMed, F1000Res) - "Accordingly, several drugs targeting the epigenome have been proposed for cancer therapy, notably, histone deacetylase inhibitors (HDACi) such as vorinostat and DNA methyltransferase inhibitors (DNMTi) such as zebularine...We found that in two cell lines (HCT116 treated with Largazole at eight doses and RH4 treated with Entinostat at 1µM) where the appropriate data (pre-treatment transcriptome and epigenome as well as post-treatment transcriptome) is available, our model distinguished the post-treatment up versus downregulated genes with high accuracy (up to ROC of 0.89)...Here we present a first assessment of the predictability of genome-wide transcriptomic changes upon treatment with HDACi. Lack of appropriate omics data from clinical trials of epigenetic drugs currently hampers the assessment of applicability of our approach in clinical setting."

Journal • Oncology

Epigenetic changes associated with Cutibacteriam acnes-induced innate immune memory events in human keratinocytes (SID 2025) - "These epigenetic differences were supported by region-specific changes in mRNA expression of TET and DNMT genes. Our findings suggest that the cutaneous microbiota induces skin region-specific IIM changes in keratinocytes and that altered epigenetic regulation may be involved in these processes."

Aesthetic Medicine • Inflammation • CXCL8 • DNMT1 • TNFA

Little to show for much effort and investment: An industry perspective on MDS drug development (MDS 2025) - "Randomized studies incorporated lenalidomide, vorinostat, entinostat (MS-275), durvalumab, valproic acid, idarubicin, eltrombopag, pevonedistat (MLN4924), eprenetapopt (APR-246), sabatolimab (MBG453), magrolimab (Hu5F9-G4), or tamibarotene (SY-1425)...While the approval of luspatercept and imetelstat for lower-risk patients provides a glimmer of hope, this track record of failure in higher-risk MDS is enough to make a prudent investor or senior pharmaceutical executive think twice before committing further resources to development in this difficult group of diseases...Nor is it because the existing therapies are so good that they're hard to beat, although the practice of giving a few cycles of azacitidine or decitabine in local clinics before referring a patient to a trial center has been an unfortunate barrier to accrual...In this session I will discuss some potential fixes for a few of these problems. But solutions to other barriers are less clear, and will require..."

Acute Myelogenous Leukemia • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • FLT3 • TP53

Systematic profiling of cancer-fibroblast interactions reveals drug combinations in ovarian cancer. (PubMed, Mol Oncol) - "Most importantly, our data identified the two drug combinations of Birinapant or Vorinostat with Carboplatin as promising treatments, exploiting the altered cancer cell phenotype in co-cultures. These findings were supported by the increased sensitivity of ex vivo cultures to these combinations."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Design, synthesis and antitumor activity evaluation of novel IMPDH II and HDAC1 dual inhibitor. (PubMed, RSC Med Chem) - "Furthermore, compound C12 exhibited acceptable in vivo pharmacokinetics of properties. In conclusion, compound C12 represents a potential new dual inhibitor targeting both hIMPDH II and HDAC1."

Journal • Oncology • HDAC1

CLINICAL EXPERIENCE WITH HDAC INHIBITOR-BASED PROTOCOLS IN MECOM-REARRANGED ACUTE MYELOID LEUKEMIA (EHA 2025) - "Patients received protocols incorporating valproic acid (n=3), vorinostat (SAHA, n=3), mocetinostat (n=2), and panobinostat (n=1).Nine patients (1%) with MECOMr were identified (median age 57 years, range 16-76). We observed a 67% response rate with HDAC inhibitor-based therapy, suggesting a potential benefit of HDAC inhibition in MECOMr-AML. Although limited by small sample size and heterogeneous HDAC inhibitor regimens, these findings warrant further investigation through dedicated clinical trials to define optimal use of HDAC inhibition strategies in this therapeutically challenging leukemia subgroup with poor prognosis and limited treatment options."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • HDAC3 • MECOM

PERSONALIZED GENETICALLY ADAPTED THERAPY FOR NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA: A SINGLE-CENTER PROSPECTIVE STUDY (EHA 2025) - "The genotype distribution in the cohort was as follows: MCD - 6%, N1 - 32%, BN2 - 6%, EZB - 15%, ST2 - 6%, and NOS - 35%.For patients assigned to the R-CHOP-X arm, they will receive rituximab 375 mg/m2 IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 2, vincristine 1,4 mg/m2 on Day 2, doxorubicin 50 mg/m2 IV on Day 2 and prednisone 100 mg/day IV on Days 1-5 of every 21-day cycle for the first cycle. For the remaining 5 cycles, they will receive either acalabrutinib on Days 1-21 (MCD/BN2/N1 subtypes), or lenalidomide on Days 1-10 (ST2/NOS subtypes), or decitabine on Days 1-5 (TP53 mutation subtypes), or vorinostat on Days 1-9 (EZB subtype), followed by standard R-CHOP of every 21-day cycle.Thirty-four patients received personalized genotype-directed therapy... The results of this clinical trial are promising and provide preliminary evidence for the benefit of personalized genotype-directed cancer therapy in untreated DLBCL. This therapeutic strategy demonstrates high..."

Clinical • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • TP53

Construction of polydopamine nanomedicine for dual inhibition and degradation of histone deacetylases in cancer cells. (PubMed, Int J Biol Macromol) - "Both in vivo and in vitro experiments indicate that PDA-SAHA NPs significantly inhibit the proliferation of cancer cells and enhance apoptotic effects, thereby effectively suppressing tumor growth. This dual mechanism, combining HDAC inhibition and photothermal-induced degradation, not only offers a novel strategy for overcoming the resistance associated with traditional HDAC inhibitors but also shows substantial potential in cancer treatment."

Journal • Oncology • Targeted Protein Degradation