quisinostat (JNJ 26481585) / J&J, ChemRar, Viriom - LARVOL DELTA

Orthotopic PDX modeling and preclinical therapeutic evaluation in pediatric ependymoma (EANO 2026) - "A targeted drug panel based on molecular alterations in ST-EPN, including CBL0137 (epigenetic inhibitor), ACT001 (NF-κB inhibitor), dovitinib and lenvatinib (VEGFR inhibitors), and entinostat and quisinostat (HDAC inhibitors) was evaluated for cytotoxicity in vitro using Alamar Blue and clonogenic assays. These orthotopic ST-EPN PDX models represent a reliable preclinical platform, enabling evaluation of molecularly guided combination therapies for pediatric ST-EPN with ZFTA-RELA fusion. Dovitinib emerged as a potential new treatment for RELA fused EPN."

Preclinical • Ependymoma • Oncology • Solid Tumor • RELA • ZFTA

HDAC1 inhibits CDX2 and promotes colorectal cancer cell migration (ECP 2026) - "Our findings identify HDAC1 as an inhibitor of CDX2 in CRC, positioning Quisinostat as a promising drug for restoring CDX2 expression and reducing cell migration in CDX2-low CRCs."

Colorectal Cancer • Oncology • Solid Tumor • CDX2

An LC-MS/MS assay for quantification of total and unbound levels of a potent HDAC inhibitor, quisinostat, in human plasma, cerebrospinal fluid, and brain tumor (SNO 2026) - No abstract available

Brain Cancer • Oncology • Solid Tumor

A Phase 0/1b clinical trial of quisinostat plus radiotherapy in recurrent glioblastoma (EANO 2026) - "Quisinostat does not achieve pharmacologically-relevant concentrations in Gd-non-enhancing tumor tissue but is detectable in CSF and tumor tissue. In Gd-enhancing tumor tissue, 33% of tumors demonstrated the expected PD response. Since no patients qualified for the Phase 1 study, this trial was terminated."

Clinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Boosting anti-leukemia cytotoxicity of CD4 and CD8 T cells through combined inhibition of MEK and HDAC. (PubMed, Blood) - "Through a drug re-purpose screen, we identified and validated that combined MEK and HDAC inhibitions via trametinib and quisinostat (TQ) potently inhibited the growth of mouse and human NRAS;ASXL1-AML (NA-AML), MLLr, and NPM1 mutated AML cells in vitro. In leukemia:T cell co-cultures, TQ-treated T cells demonstrated greatly improved MHC-dependent leukemia killing. Our findings suggest that the dual actions of TQ on NA-AML and T cells enhance leukemia recognition and anti-leukemia killing of endogenous T cells, leading to effective AML clearance."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ASXL1 • CD4 • CD8 • CIITA • NPM1 • NRAS • STAT1

Development of orthotopic PDX models and discovery of targeted therapies in pediatric ependymoma (ISPNO 2026) - "Targeted agents were selected based on molecular alterations in relapsed zccs1304 tumors and assessed for therapeutic efficacy, including FACT inhibitor (CBL0137), NF-κB inhibitor (ACT001), VEGFR inhibitors (dovitinib, lenvatinib) and HDAC inhibitors (entinostat, quisinostat). Additionally, dovitinib in combination with CBL0137 or quisinostat significantly enhanced cytotoxicity in cultures. Our orthotopic ST-EPN PDX models offer a reliable preclinical platform for developing rational combination therapies for pediatric ST-EPN with ZFTA-RELA fusion."

Clinical • Ependymoma • Oncology • Pediatrics • Solid Tumor • RELA • ZFTA

HDAC INHIBITORS SUPPRESS SURVIVAL OF NEOPLASTIC MAST CELLS AND COUNTERACT CYTOKINE-INDUCED UPREGULATION OF IMMUNE CHECKPOINT MOLECULES PD-L1, CD47 AND TIM-3 (EHA 2026) - "In most patients, SM is associated with the KIT D816V mutation, which confers resistance to multiple tyrosine kinase inhibitors (TKIs), including imatinib...Moreover, combinations of HDAC inhibitors (panobinostat or quisinostat) and KIT-targeting drugs (midostaurin or avapritinib) produced cooperative growth-inhibitory effects in all HMC-1 and ROSA subclones...These findings identify HDAC inhibition as a promising therapeutic strategy in advanced SM. Whether these drugs can be successfully applied in vivo in patients with advanced SM needs to be determined in clinical studies."

IO biomarker • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • CD47 • HAVCR2 • HDAC1 • HDAC2 • MYC • PD-L1

Acute and long-term responses to treatment with the HDAC inhibitor quisinostat in preclinical models of glioblastoma (AACR 2024) - "Quisinostat treatment induces a shift in tumor cells towards a neuronal-like cell fate. Considering that GSCs have been shown to establish synaptic junctions with healthy neurons to evoke enhanced excitatory currents within glioma cells and contribute to treatment resistance, further investigation of this shift upon HDAC inhibition is crucial. Ongoing studies are aimed at evaluating the significance of these cellular and molecular changes resulting from quisinostat treatment and whether the quisinostat-induced cell fate changes can be exploited for future combination therapy for GBM."

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • HDAC1

Combined inhibition of MEK and HDACs improves the cytotoxicity of CD4 and CD8 T cells in NRAS; ASXL1-driven acute myeloid leukemia mice (AACR 2025) - "Targeting hyperactive RAS/MEK signaling via trametinib (T, a MEK inhibitor) attenuates the exhaustion of CD8 T cells and prolongs the survival of NA-AML mice. To further boost the efficacy of T, we performed a re-purpose screen of ~2,500 drugs, either approved by FDA for treating various human diseases or currently under clinical evaluation, in the absence or presence of T. We identified that quisinostat (Q), a 2nd generation of HDAC inhibitor, potently inhibited the growth of both mouse and human NA leukemia cells and significantly synergized with T in vitro...We are currently pursuing the underlying molecular mechanisms. Our data provide a strong rationale to develop immunotherapies via epigenetic modulation of both leukemia and leukemia-associated T cells."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ASXL1 • CD4 • CD8 • CD80 • CD86 • CXCR3 • CXCR5 • NRAS • PD-L1

Combined HDAC and ATM inhibition potentiates anticancer effects in glioblastoma preclinical models (AACR 2025) - "Here, we evaluated synergistic effect of combining HDAC and DNA repair enzyme, ataxia telangiectasia mutated (ATM) inhibitors, quisinostat (QST) and AZD1390 to broaden therapeutic window for GBM treatment. In vitro dose-response assays were performed in patient-derived xenograft (PDX)-derived glioma stem cells (GSCs) with both QST and AZD1390 with or without radiation treatment to assess synergy. Our data indicate that QST and AZD1390 act synergistically to radiosensitize GBM cells and increase the therapeutic window for treatment. In vivo experiments are under way to examine efficacy of this combination using orthotopic PDX GBM models. Keywords: glioblastoma, ATM, HDAC, DNA damage repair"

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CASP3

Targeting histone deacetylation, cell cycle regulators and heat shock proteins as novel therapeutic strategies for penile cancers. (PubMed, NPJ Precis Oncol) - "A paclitaxel, ifosfamide, and cisplatin-based regimen achieves response rates around 65%...Compared to standard chemotherapy (e.g. cisplatin, 5-FU, ifosfamide, irinotecan), treatment with romidepsin, quisinostat (HDAC inhibitors (i)), palbociclib (CDK4/6i), or 17-AAG and PU-H71 (HSP90i) reduced cell viability, induced apoptosis, and led to G2 / M cell cycle arrest in most PeCa cells. This research underscores the therapeutic potential of using HDAC, CDK4/6, and HSP90 inhibitors for PeCa management and reveals additional promising targets and biomarkers for future strategies."

Journal • Genito-urinary Cancer • Oncology • Penile Cancer • Solid Tumor • CDC37 • HIF1A

Synergy evaluation of quisinostat (HDAC I Inhibitor) and ZE94-0605 (CDK2 Inhibitor) in various in vitro and in vivo models (AACR 2026) - "Combining quisinostat with the CDK2 inhibitor ZE94-0605 yields synergistic efficacy and superior outcomes in the OVCAR-3 xenograft model. Our findings indicate that quisinostat enhances in vivo therapeutic efficacy and supports further evaluation of this combination strategy for ovarian and other cancers."

Preclinical • Brain Cancer • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor

Phase 0 With Expansion Phase Clinical Trial of Quisinostat Plus Radiotherapy in Newly-diagnosed and Recurrent Grade 4 IDH-Wildtype Glioblastomas (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Nader Sanai | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2029 ➔ Jan 2028 | Trial primary completion date: Jul 2027 ➔ Jul 2026

Enrollment closed • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Comprehensive molecular profiling of penile carcinoma reveals histone deacetylation, cell cycle regulators and heat shock proteins as targetable therapeutic strategies (DKK 2026) - "Current treatment options include surgery, radiotherapy, and the TIP regimen (paclitaxel, ifosfamide, cisplatin), despite the latter achieving moderate response rates of 15 - 55 %...Functional assays assessed the efficacy of standard chemotherapeutic drugs as compared to inhibitors targeting HDAC (romidepsin, quisinostat), CDK4/6 (palbociclib, ribociclib), and HSP90 (17-AAG, PU-H71)... Compared to standard therapeutic agents such as cisplatin, 5-FU, ifosfamide, and irinotecan, treatment with romidepsin, quisinostat, palbociclib, 17-AAG, and PU-H71 notably reduced viability, induced apoptosis, and caused an accumulation in the G2 / M cell cycle phase in most PeCa cell lines. Our findings highlight HDAC, CDK4/6, and HSP90 inhibitors as promising therapeutic options for PeCa while providing a resource for novel putative biomarker and future targeted therapies."

Genito-urinary Cancer • Oncology • Penile Cancer • Solid Tumor • ANXA5 • CDC37 • HIF1A

Macrophage TRIM21 Inhibition Ameliorates Murine Acute Pancreatitis via PHB2-Mediated Mitochondrial Stabilization. (PubMed, Adv Sci (Weinh)) - "Additionally, pharmacological inhibition of TRIM21 with quisinostat mitigates AP progression. Our findings reveal the critical role of TRIM21 in AP-associated inflammation, providing a potential therapeutic strategy for inflammatory pancreatic diseases."

Journal • Preclinical • Inflammation • Pancreatitis • Targeted Protein Degradation • STING • TRIM21

Improved quantitative structure-activity relationship (QSAR) models to predict the activity of hydroxamic acids as HDAC inhibitors against malaria parasites. (PubMed, Eur J Med Chem) - "External validation using 106 quisinostat-derived compounds from published sources demonstrated improved accuracy of B7 and B8 (>67 %) compared to A7 (∼5 %), the best first-generation model...Moreover, the ability of these QSAR models to triage hydroxamic acid-based compounds with activity against malaria parasites was demonstrated by the identification of three potent antiplasmodial hits (PfIC50 8, 14 and 80 nM), two of which were shown to hyperacetylate P. falciparum histone H4 indicating deacetylase inhibition. These data demonstrate the potential of QSAR models to identify HDAC inhibitors for malaria drug discovery."

Journal • Infectious Disease • Malaria

Discovery of γ-Tetrahydrocarboline Derivatives as Plasmodium falciparum Histone Deacetylase Inhibitors for Treatment of Malaria. (PubMed, J Med Chem) - "Quisinostat was identified as a Plasmodium falciparum histone deacetylase 1 (PfHDAC1) inhibitor against drug-resistant malaria parasites but suffered from intolerable toxicity...Mechanistic studies showed that 5ac could downregulate the expression of malaria invasion-related genes. Overall, this study establishes γ-tetrahydrocarboline derivatives as new structurally promising PfHDAC-targeted antimalarial agents."

Journal • Infectious Disease • Malaria

HDAC and CDK inhibitor combinations suppress neutrophil activation in myeloma (ASH 2025) - "To overcome translational barriers associated with dinaciclib and entinostat, we evaluated next-generation agents: KB0742, a selective and orally bioavailable CDK9 inhibitor, in combination with quisinostat or zabadinostat , two potent HDAC inhibitors with more favorable pharmacokinetic and safety profiles. These transcriptional changes, accompanied by increased re-expression of tumor suppressors (e.g.,p16) and TGFβ/SMAD signaling components, would predict reprogramming of an anti-inflammatory microenvironment by these combination treatments in myeloma. These findings point to a promising but underdeveloped therapeutic avenue whereby suppressing neutrophil-driven inflammation enhances anti-myeloma immunity."

Hematological Malignancies • Multiple Myeloma • Smoldering Multiple Myeloma • BCL2L1 • CXCL1 • CXCL8 • IL1A • IL23A • ITGAM • NRAS • SDC1

Boosting anti-tumor immunity in NRAS; ASXL1-driven Acute Myeloid Leukemia through combined inhibition of MEK and HDACs. (ASH 2025) - "Targeting hyperactive RAS/MEK signaling viatrametinib (Tra, a MEK inhibitor) attenuated T cell exhaustion and prolonged the survival of NA-AML mice,cementing the role of T cells in modulating AML treatment outcomes...We identified and validated inhibition ofMEK/ERK signaling via Tra and histone deacetylases (HDACs) via quisinostat (Qui, a 2nd generation ofHDAC inhibitor) as an effective combo therapy against mouse and human primary NA-AML cells and non-NA human AML cell lines in vitro...Our results suggest that we must seek additionalMHC-independent anti-cancer mechanisms to further improve the therapeutic effects of TQ. We arecurrently evaluating the effects of combining TQ with anti-TIGIT immune checkpoint blockade to activateendogenous non-MHC restricted natural killer cells in NA-AML mice."

IO biomarker • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ASXL1 • CD4 • CD8 • CIITA • IL2 • NRAS • TIGIT

HDAC inhibition–induced neuronal-like state creates cytoskeletal vulnerabilities in glioblastoma. (SNO 2025) - "Quisinostat (QST), a brain-penetrant histone deacetylase inhibitor (HDACi), significantly prolongs survival when combined with radiation in patient-derived GBM models...These findings reveal that HDACi treatment paradoxically promotes survival through a reprogrammed neuronal-like state while creating exploitable structural vulnerabilities. This work provides mechanistic insight into GBM's adaptive resistance strategies and identifies cytoskeletal targeting as a rational combination approach to overcome HDACi resistance."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • GRIK2 • TUBB3

HDAC inhibition enhances medulloblastoma immunogenicity and prolongs survival in preclinical models (SNO 2025) - "Ongoing studies are aimed at profiling transcriptional responses and chromatin accessibility following quisinostat treatment to better define mechanisms of action of the drug, and to identify synergistic therapeutic combinations. These data provide a strong rationale for developing HDAC inhibitor-based combination therapies to overcome immune resistance in medulloblastoma."

IO biomarker • Preclinical • Tumor mutational burden • Brain Cancer • Medulloblastoma • Solid Tumor • LGALS9 • TAP1 • TMB

High-throughput screening identifies the activity of histone deacetylase inhibitors in patient-derived models of soft tissue sarcoma. (PubMed, Cancer Biol Ther) - "Quisinostat also showed potent activity in leiomyosarcoma (LMS) cell lines (5.82-31.32 nM), which represent an additional complex karyotype soft tissue sarcoma. Quisinostat demonstrated strong preclinical activity and synergy with standard-of-care doxorubicin in models of UPS and LMS."

Journal • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • EPAS1 • FOSL1

Chrono-Pharmacology for Cancer: Harnessing Circadian Regulations of the Cell Cycle and Immune Response Dynamics for Precision Therapy. (PubMed, ACS Pharmacol Transl Sci) - "We discussed some interesting examples, like HSP90 inhibitors (ganetespib), HDAC inhibitors (quisinostat), topoisomerase inhibitors (doxorubicin), and BCL-2 family antagonists (Obatoclax, TW-37), whose therapeutic activities are tightly regulated by circadian control over their molecular targets, pharmacokinetic processes, and downstream physiological pathways. Furthermore, the circadian influence extends to the tumor microenvironment and antitumor immunity, suggesting novel chrono-immunotherapy approaches. By putting together the molecular bases of these temporal dynamics, this review underscores the significant potential of chronotherapythe timed administration of drugs to improve cancer treatment by enhancing therapeutic indices and paving the way for personalized, temporally optimized oncology strategies."

Journal • Review • Oncology • Targeted Protein Degradation • ARNTL • BCL2 • BMAL1 • CDC37 • CDKN1A • FBXW7

HDAC inhibition–induced neuronal-like state creates cytoskeletal vulnerabilities in glioblastoma. (WFNOS 2025) - "Quisinostat (QST), a brain-penetrant histone deacetylase inhibitor (HDACi), significantly prolongs survival when combined with radiation in patient-derived GBM models...These findings reveal that HDACi treatment paradoxically promotes survival through a reprogrammed neuronal-like state while creating exploitable structural vulnerabilities. This work provides mechanistic insight into GBM's adaptive resistance strategies and identifies cytoskeletal targeting as a rational combination approach to overcome HDACi resistance."

Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • GRIK2 • TUBB3

HDAC inhibition enhances medulloblastoma immunogenicity and prolongs survival in preclinical models (WFNOS 2025) - "Ongoing studies are aimed at profiling transcriptional responses and chromatin accessibility following quisinostat treatment to better define mechanisms of action of the drug, and to identify synergistic therapeutic combinations. These data provide a strong rationale for developing HDAC inhibitor-based combination therapies to overcome immune resistance in medulloblastoma."

IO biomarker • Preclinical • Tumor mutational burden • Brain Cancer • Medulloblastoma • Solid Tumor • LGALS9 • TAP1 • TMB