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

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

A phase II trial of quisinostat for high-risk uveal melanoma (ESMO 2025) - P2 | "Legal entity responsible for the study University of Miami. Funding Mandell Family Foundation, Viriom, Inc (drug only)."

P2 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1 • HDAC4

Inhibition of Histone Deacetylases Induces Cancer Cell Apoptosis Through the PERK Pathway of ER Stress Response. (PubMed, J Cell Mol Med) - "In addition, a non-phosphorylatable mutant of eIF2α, a critical substrate that transduces the PERK-mediated ER stress response, abolishes apoptosis induced by HDACi, but not by the DNA damage reagent doxorubicin. HDACi reduce the sizes of tumours formed from wildtype but not eIF2αS51A-mutant cells in a xenograft model, further demonstrating the involvement of the PERK subbranch in HDACi-induced ER stress and cell death. Our study reveals novel effects of the well-studied family of HDAC inhibitors, which can be explored further in clinics to treat certain types of cancer manifested with abnormal ER stress conditions."

Journal • Oncology • ATF6

Whole-process 3D ECM-encapsulated organoid-based automated high-throughput screening platform accelerates drug discovery for rare diseases. (PubMed, Life Med) - "The representative candidate, Quisinostat 2HCl, demonstrated significantly stronger anti-tumor efficacy than clinically used agents in vivo. This platform significantly improves the rapidity and efficiency of 3D ECM-encapsulated organoid drug screening and facilitates new drug discovery for rare diseases."

Journal • Cervical Cancer • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Rare Diseases • Solid Tumor

Epigenetic potentiation of 5-fluorouracil by HDAC inhibitor quisinostat enhances antitumor effects in colorectal cancer. (PubMed, Cancer Cell Int) - No abstract available

Journal • Colorectal Cancer • Oncology • Solid Tumor

Epigenetic potentiation of 5-fluorouracil by HDAC inhibitor quisinostat enhances antitumor effects in colorectal cancer (Biomed Central) - "Quisinostat significantly increased H3K27 acetylation and enhanced the cytotoxic effect of 5-FU by lowering its IC50 in both cell lines. The combination treatment markedly suppressed proliferation, as evidenced by reduced Ki-67 expression. Quisinostat in combination with 5-FU significantly enhanced ΔΨm loss and apoptotic cell death. Furthermore, the combination treatment inhibited cell migration and reversed the EMT phenotype by increasing E-cadherin and decreasing N-cadherin expression."

Preclinical • Colorectal Cancer

The molecular characterization of penile carcinomas for the identification of new therapeutic targets (DGU 2025) - "This study accentuates the cytotoxic efficacy of inhibitors targeting HDAC, CDK4/6, or HSP90 as novel strategies for the treatment and identification of PeCa."

Genito-urinary Cancer • Oncology • Penile Cancer • Solid Tumor • Urethral Cancer • ANXA5 • CDC37 • CDK4 • HIF1A • HSP90AA1

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 | Recruiting | Sponsor: Nader Sanai | Not yet recruiting ➔ Recruiting | Trial completion date: May 2027 ➔ Jan 2029 | Initiation date: May 2025 ➔ Sep 2025 | Trial primary completion date: May 2026 ➔ Jul 2027

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

HDAC and CDK Inhibitor Combinations Synergize in Limiting Myeloma (IMS 2025) - "Further investigation into a combined genetic signature will aid in discovering mechanisms of drug synergy and provide biomarkers for a combined response that may translate to the clinic."

Late-breaking abstract • Hematological Malignancies • Multiple Myeloma • ANXA5 • BCL2L1 • CDK1 • HDAC1 • MYC • SDC1

In vitro and in vivo activity of quisinostat against Toxoplasma gondii. (PubMed, Antimicrob Agents Chemother) - "The current gold-standard treatment, a combination of pyrimethamine and sulfadiazine, is limited by severe adverse events, necessitating the development of novel therapeutic agents. In mice infected with low-virulent ME49 tachyzoites, quisinostat treatment decreased parasite burden in multiple organs and increased the survival to 80%. Taken together, these findings demonstrate that quisinostat has potent anti-Toxoplasma activity both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis."

Journal • Preclinical • Infectious Disease • HDAC3

A propidium iodide-based in vitro screen of the "Bug Box" against Babesia duncani reveals potent inhibitors. (PubMed, Antimicrob Agents Chemother) - "A screen of the 41-compound library Structural Genomics Consortium Bug Box was conducted, yielding five hits: trimethoprim, atovaquone, SDDC M7, diphenyleneiodonium chloride, and panobinostat. Dose-response testing of structurally related compounds revealed multiple potential leads, including nanatinostat and quisinostat, both of which were potent at the nanomolar level and showed favorable selectivity index in cytotoxicity studies. High-throughput screening using PI and 384-well plates is an advance in drug discovery for babesiosis, and HDAC inhibitors show promise as lead compounds worthy of further investigation."

Journal • Preclinical • Infectious Disease

Adjuvant Quisinostat in High-Risk Uveal Melanoma (clinicaltrials.gov) - P2 | N=63 | Recruiting | Sponsor: University of Miami | Not yet recruiting ➔ Recruiting

Enrollment open • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

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

Adjuvant Quisinostat in High-Risk Uveal Melanoma (clinicaltrials.gov) - P2 | N=63 | Not yet recruiting | Sponsor: University of Miami

New P2 trial • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia. (PubMed, Hemasphere) - "Importantly, H1-0 protein levels correspond to susceptibility of BCP-ALL cells towards histone deacetylase inhibitors (HDACis) and combinatorial treatment using the H1-0-inducing HDACi Quisinostat showed promising synergism with established chemotherapeutic drugs. Taken together, our data identify H1-0 as a key regulator of the ETV6::RUNX1+ transcriptome and indicate that the addition of Quisinostat may be beneficial to target non-responsive or relapsing ETV6::RUNX1+ BCP-ALL."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Pediatrics • ETV6 • RAG1 • RUNX1

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 | Not yet recruiting | Sponsor: Nader Sanai

New P1 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

A high-throughput, microplate reader-based method to monitor in vitro HIV latency reversal in the absence of flow cytometry. (PubMed, Virology) - "We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry. Using this method, we screen 79 epigenetic modifiers and identify CUDC-101, molibresib, and quisinostat as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease • CD4