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

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

Central nervous system distributional kinetics of selected histone deacetylase inhibitors. (PubMed, J Pharmacol Exp Ther) - "To gain further context for these findings, the CNS distributional kinetics for vorinostat and quisinostat were compared with another hydroxamic acid HDACI, panobinostat. Employing techniques that minimize the postsampling degradation in plasma, brain, and spinal cord, accurate CNS distributional kinetic parameters for these potentially useful compounds were determined. A knowledge of CNS exposure, time to peak, and duration can inform dosing strategies in preclinical and clinical trials in selected CNS tumors."

Journal • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Solid Tumor

Treatment with TNFα and lipolysis-stimulated lipoprotein receptor (LSR) antibody in the presence of HDAC inhibitors promotes apoptosis in human salivary duct adenocarcinoma. (PubMed, Tissue Barriers) - "A253 cells were treated with human recombinant TNFα with or without HDAC inhibitor trichostatin A (TSA) and quisinostat (JNJ-26481585). The tricellular signaling pathway JNK inhibitor SP600125 and Hippo pathway MST1/2 inhibitor XMU-MP-1 prevented the apoptosis induced by treatment using TNFα or LSR-N-ab with HDAC inhibitors. Our findings indicated that treatment with TNFα or LSR-N-ab with HDAC inhibitors might be useful in the therapy for human SDC by enhancing apoptosis."

Journal • Metabolic Disorders • Oncology • Salivary Gland Cancer • LSR • TNFA

Multicomponent syntheses enable the discovery of novel quisinostat-derived chemotypes as histone deacetylase inhibitors. (PubMed, Eur J Med Chem) - "Furthermore, these compounds caused hyperacetylation of histone H3 and α-tubulin, indicating robust cellular target engagement. Overall, in this work we have identified the HDAC inhibitor 18b with selective antiplasmodial and 9b, 9d, and 13f with selective anticancer activities, providing valuable hits for further drug development efforts aimed at creating derivatives with reduced cytotoxicity against non-cancer cells compared to quisinostat."

Epigenetic controller • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Head and Neck Cancer • Hepatocellular Cancer • Infectious Disease • Malaria • Oncology • Ovarian Cancer • Solid Tumor • CASP3 • CASP7 • HDAC1

TRIM21-mediated ubiquitination and phosphorylation of ERK1/2 promotes cell proliferation and drug resistance in pituitary adenomas. (PubMed, Neuro Oncol) - "TRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment."

Journal • Oncology • Pituitary Gland Carcinoma • Targeted Protein Degradation • MAP2K1 • TRIM21

Design, synthesis and therapeutic evaluation of novel antimalarial derivatives based on the clinical antitumor candidate drug Quisinostat. (PubMed, Bioorg Med Chem) - "Furthermore, compounds 33 and 37 also displayed significant antimalarial therapeutic effect and improved animal safety in rodent malaria model. Collectively, 33 and 37 were structurally novel PfHDAC inhibitors and promising antimalarial lead compounds for the next generation of antimalarial drug research."

Journal • Infectious Disease • Malaria • Oncology

The nucleosome remodeling and deacetylase complex underlies selective dependency in H3 G34-mutant diffuse hemispheric glioma (SNO 2024) - "To therapeutically target NuRD-associated class I HDAC activity, patient-derived H3 G34-mutant DHG cell lines were treated with quisinostat, a highly potent class I and II HDAC inhibitor...Ongoing experiments are evaluating dependencies in vivo. Our results may suggest a differential requirement for chromatin repressive complex dysregulation in the pathogenesis of oncohistone-mutant pediatric-type diffuse high-grade gliomas."

Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • Malignant Glioma • Oncology • Pediatrics • Solid Tumor

High throughput screening identified the activity of histone deacetylase inhibitors in patient-derived models of undifferentiated pleomorphic sarcoma (EORTC-NCI-AACR 2024) - "Of four HDAC inhibitors with the lowest average IC50 values (romidepsin, 1.3 nM; CUDC-907, 6.5 nM; panobinostat, 15.6 nM; and quisinostat, 26.2 nM), quisinostat exhibited the most promising synergistic effects with doxorubicin in vitro. In vivo investigations into the anti-tumour response of patient-derived xenograft models of UPS to quisinostat, alone or in combination with doxorubicin, are ongoing. ConclusionQuisinostat demonstrates potent anti-tumour activity in patient-derived models of UPS in vitro, with an enhanced response when doxorubicin is added."

Clinical • Epigenetic controller • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma

Reversal of epigenetic dysregulation in breast cancer brain metastasis via HDAC1/2 inhibition (EANO 2024) - "Our findings establish the REST/HDAC axis as a key promoter of BCBM. Quisinostat, by specifically inhibiting HDAC1/HDAC2, demonstrated significant effectiveness, indicating its potential as a management strategy for brain metastases. This approach underscores the promise of HDAC inhibitors with enhanced selectivity and brain penetration as emerging tools in neuro-oncology."

Breast Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • HDAC2 • TGFB1

A high-throughput, microplate reader-based method to monitor in vitro HIV latency reversal in the absence of flow cytometry. (PubMed, bioRxiv) - "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 molibresib, quisinostat, and CUDC-101 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. J-Lat T-cell lines are important to HIV cure research but require flow cytometryWe describe a method to work with J-Lat cells using a standard microplate readerThis assay can detect control LRAs similar to flow cytometry and discover new LRAsThis assay allows low-resourced laboratories to contribute to HIV cure research."

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

Utilizing Epigenetic Regulators to improve HSC-based lentiviral gene therapy. (PubMed, Blood Adv) - "The HDAC inhibitor Quisinostat and the bromodomain inhibitor CPI203 each promote ex vivo expansion of functional HSCs, as validated by xenotransplantation assays and single cell RNA-sequencing analysis. Of note, we demonstrated that addition of Quisinostat improved LV transduction efficiency of HSCs and early progenitors. Our suggested culture conditions highlight the potential therapeutic effect of epigenetic regulators in hematopoietic stem cell biology and their clinical applications to advance HSC-based gene correction."

Gene therapy • Journal • Gene Therapies • Transplantation

NOVEL EPIGENETIC BASED DIFFERENTIATION THERAPY FOR ACUTE MYELOID LEUKEMIA (EHA 2024) - "Cell differentiationinduced by our compounds was significantly more pronounced that differentiation induced by referenceHDACi such as Panobinostat, Vorinostat, Entinostat, Tubastatin or Quisinostat (Fig. We have developed and characterized CM-444 and CM-1758, two novel and potent DACi with high capacityfor inducing myeloid differentiation at low non-cytotoxic doses, both in vitro and in vivo, in different AMLsubtypes. Both compounds showed a mechanism of action different from other DACi, which was mediated bythe acetylation of non-histone proteins related to the enhancer-promoter chromatin regulatory complex. Thesecompounds represent a novel and promising approach for a differentiation-based therapy for testing in AMLpatients."

Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CEBPA • GATA2 • MYC • SPI1

New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma. (PubMed, J Cell Mol Med) - "Thus, we investigated the effect of the second generation HDAC inhibitor (HDACi) quisinostat in five UC cell lines (UCC) and two normal control cell lines in comparison to romidepsin, a well characterized HDACi which was previously shown to induce cell death and cell cycle arrest. These combinations appeared to be well tolerated in normal cells. In conclusion, our results suggest new promising combination regimes for treatment of UC, also in the cisplatin-resistant setting."

Combination therapy • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Central Nervous System Distributional Kinetics of Selected Histone Deacetylase Inhibitors. (PubMed, J Pharmacol Exp Ther) - "To gain further context for these findings, the CNS distributional kinetics for vorinostat and quisinostat were compared to another hydroxamic acid HDACI, panobinostat. Employing techniques that minimize the post-sampling degradation in plasma, brain and spinal cord, accurate CNS distributional kinetic parameters for these potentially useful compounds were determined. A knowledge of CNS exposure (Kp,uu), time to peak, and duration can inform dosing strategies in preclinical and clinical trials in selected CNS tumors."

Epigenetic controller • Journal • Brain Cancer • Breast Cancer • CNS Tumor • Metabolic Disorders • Oncology • Solid Tumor

A comprehensive characterization of the dehydrogenase-reductase DHRS2 and its involvement in histone deacetylase inhibition. (PubMed, Exp Cell Res) - "With the emphasis on urologic malignancies (testicular germ cell tumors, urothelial-, prostate-, and renal cell carcinoma), this study concluded that elevated DHRS2 levels could be indicative of a successful HDACi treatment and, thereby offering a novel putative predictive biomarker."

Epigenetic controller • Journal • Genito-urinary Cancer • Germ Cell Tumors • Metabolic Disorders • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Testicular Cancer • Urology • Urothelial Cancer • DHRS2

Targeting Epigenetic and Post-translational Modifications Regulating Pyroptosis for the Treatment of Inflammatory Diseases. (PubMed, Pharmacol Res) - "We also illustrate these within pyroptosis-associated inflammatory diseases. In addition, we discuss the effects of novel therapeutic strategies targeting epigenetic and post-translational modifications on pyroptosis, and provide prospective insight into the regulation of pyroptosis for the treatment of inflammatory diseases."

Journal • Review • CNS Disorders • Diabetes • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Oncology • Rheumatology • Targeted Protein Degradation

Current knowledge of ferroptosis in the pathogenesis and prognosis of oral squamous cell carcinoma. (PubMed, Cell Signal) - "Several specific interventions (i.e., Quisinostat, Carnosic acid, hyperbaric oxygen, melatonin, aqueous-soluble sporoderm-removed G. lucidum spore powder, and disulfiram/copper complex) were found to dramatically induce ferroptosis cell death of OSCC via multiple mechanisms. This review highlighted the pivotal role of ferroptosis in the pathogenesis and prognosis of OSCC. Future anticancer therapeutic strategies targeting ferroptosis and its associated molecules might provide a new insight for OSCC treatment."

Journal • Review • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • AEBP1 • GPX4 • miR-125b • PER1

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

ΔNp63 regulates MDSC survival and metabolism in triple-negative breast cancer. (PubMed, iScience) - "In current studies, targeting ΔNp63 with inducible CRISPR knockout and Histone deacetylase inhibitor Quisinostat showed that ΔNp63 is important for tumor progression and metastasis in established tumors by promoting myeloid-derived suppressor cell (MDSC) survival through tumor necrosis factor alpha...We further demonstrated that targeting ΔNp63 sensitizes chemotherapy. Overall, we showed that ΔNp63 reprograms the MDSC-mediated immunosuppressive functions in TNBC, highlighting the benefit of targeting ΔNp63 in chemotherapy-resistant TNBC."

Journal • Myeloid-derived suppressor cells • Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • FOXP3 • TNFA

The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells. (PubMed, Int J Mol Sci) - "Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CGN • CLDN2 • CLDN4 • FOXO1