^
    1d
    Optimization of Epigenetic Modifier Drug Combination for Synergistic Effect against Glioblastoma Multiform Cancer Cell Lines. (PubMed, Cancer Invest)
    Cell lines were treated with SAHA, 5-Azacytidine, GSK-126, and PTC-209 individually and then RSM was used to find most effective combinations. Results showed that optimized combinations significantly reduce cell survival and induce cell cycle arrest and apoptosis in both cell lines. Expression of cyclin B1 and cyclin D1 were decreased while caspase3 increased expression.
    Preclinical • Journal
    |
    CCND1 (Cyclin D1) • CASP3 (Caspase 3) • CCNB1 (Cyclin B1)
    |
    CCND1 expression
    |
    azacitidine • Zolinza (vorinostat) • GSK2816126 • PTC-209
    4d
    Evaluation of 1,10-phenanthroline-based hydroxamate derivative as dual histone deacetylases/ribonucleotide reductase inhibitor with antitumor activities. (PubMed, Daru)
    The present study emphasizes the prospect of designing a potential 1,10-phenanthroline hydroxamic acid derivative as a novel dual HDAC and RR-inhibiting anti-cancer molecule.
    Journal • Epigenetic controller
    |
    RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) • HDAC7 (Histone Deacetylase 7)
    |
    Zolinza (vorinostat)
    8d
    Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas (clinicaltrials.gov)
    P1, N=83, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Apr 2025
    Trial completion date • Combination therapy
    |
    temozolomide • Zolinza (vorinostat)
    8d
    Apigenin and its combination with Vorinostat induces apoptotic-mediated cell death in TNBC by modulating the epigenetic and apoptotic regulators and related miRNAs. (PubMed, Sci Rep)
    Molecular docking and MD simulations explored the mechanism of catalytic inhibition of HDAC1 and HDAC3 and supported the in-vitro studies. The overall studies demonstrated an anti-TNBC potential of Apigenin and may help to design an effective strategy to treat metastatic phenotype of TNBC.
    Journal
    |
    MIR200B (MicroRNA 200b) • HDAC1 (Histone Deacetylase 1) • HDAC3 (Histone Deacetylase 3)
    |
    Zolinza (vorinostat)
    9d
    Design, synthesis, insilco study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors. (PubMed, Pol Merkur Lekarski)
    The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.
    Journal • Epigenetic controller
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    Zolinza (vorinostat)
    10d
    Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: mechanisms, therapeutic implications, and future perspectives. (PubMed, Exp Hematol Oncol)
    Four drugs in this category have received approval from the U.S. Food and Drug Administration (FDA) for use: Panobinonstat (though canceled by the FDA in 2022), Vorinostat, Belinostat and Romidepsin. This review provides a comprehensive evaluation of the clinical efficacy and safety data pertaining to the currently approved histone deacetylase inhibitors, as well as an explanation of the crucial function of histone deacetylase in multiple myeloma and the characteristics of the different histone deacetylase inhibitors. Moreover, it provides a concise overview of the most recent developments in the use of histone deacetylase inhibitors for treating multiple myeloma, as well as potential future uses in treatment.
    Review • Journal • Epigenetic controller
    |
    BCL2 (B-cell CLL/lymphoma 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    Zolinza (vorinostat) • Istodax (romidepsin) • Beleodaq (belinostat)
    10d
    High-Dose or Low-Dose Vorinostat in Combination With Carboplatin or Paclitaxel in Treating Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=20, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date • Combination therapy • Metastases
    |
    carboplatin • paclitaxel • Zolinza (vorinostat)
    10d
    Suberanilohydroxamic acid (SAHA), a HDAC inhibitor, suppresses the effect of Treg cells by targeting the c-Myc/CCL1 pathway in glioma stem cells and improves PD-L1 blockade therapy. (PubMed, J Neurooncol)
    SAHA inhibited the binding of c-Myc with the CCL1 promoter and then suppressed the transcription of CCL1.Additionally, it effectively blocked the interplay of CCL1-CCR8, resulting in reduced activity of Tregs and alleviation of tumor immunosuppression.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • HDAC2 (Histone deacetylase 2) • CCR8 (C-C Motif Chemokine Receptor 8)
    |
    Zolinza (vorinostat)
    20d
    Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation. (PubMed, Nat Commun)
    Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.
    Journal
    |
    SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)
    |
    SF3B1 mutation • SRSF2 mutation • U2AF1 mutation
    |
    Zolinza (vorinostat)
    23d
    Vorinostat, temozolomide or bevacizumab with irradiation and maintenance BEV/TMZ in pediatric high-grade glioma: A Children's Oncology Group Study. (PubMed, Neurooncol Adv)
    Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • TERT (Telomerase Reverse Transcriptase) • TERC (Telomerase RNA Component)
    |
    PIK3CA mutation • PTEN mutation
    |
    Avastin (bevacizumab) • temozolomide • Zolinza (vorinostat)
    25d
    Ketogenic diet alters the epigenetic and immune landscape of prostate cancer to overcome resistance to immune checkpoint blockade therapy. (PubMed, Cancer Res)
    In this study, we established a series of ICB-resistant PCa cell lines and developed a highly effective strategy of combining anti-PD1 and anti-CTLA4 antibodies with histone deacetylase inhibitor (HDACi) vorinostat, a cyclic ketogenic diet (CKD), or dietary supplementation of the ketone body β-hydroxybutyrate (BHB), which is an endogenous HDACi...Single-cell transcriptomic and proteomic profiling revealed that HDACi and ketogenesis enhanced ICB efficacy through both cancer cell-intrinsic mechanisms, including upregulation of MHC class I molecules, and -extrinsic mechanisms, such as CD8+ T cell chemoattraction, M1/M2 macrophage rebalancing, monocyte differentiation toward antigen presenting cells, and diminished neutrophil infiltration. Overall, these findings illuminate a potential clinical path of using HDACi and optimized KD regimens to enhance ICB therapy for PCa.
    Journal • Checkpoint inhibition • Checkpoint block
    |
    CD8 (cluster of differentiation 8)
    |
    Zolinza (vorinostat)
    26d
    Vorinostat and 177Lu-PSMA-617 for the Treatment of PSMA-Low Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov)
    P2, N=15, Not yet recruiting, University of Washington | Initiation date: Apr 2024 --> Aug 2024
    Trial initiation date • Metastases
    |
    Zolinza (vorinostat) • Pluvicto (lutetium Lu 177 vipivotide tetraxetan)
    28d
    A novel potent class I HDAC inhibitor reverses the STAT4/p66Shc apoptotic defect in B cells from chronic lymphocytic leukemia patients. (PubMed, Biomed Pharmacother)
    6c (chlopynostat) was identified as a potent HDAC1i with a superior profile over entinostat...To sum up, HDAC1 inhibition is necessary to reactivate STAT4/p66Shc expression in patients with CLL. 6c is one of the most potent HDAC1is known to date and represents a novel pharmacological tool for reversing the impairment of the STAT4/p66Shc apoptotic machinery.
    Journal
    |
    HDAC3 (Histone Deacetylase 3) • STAT4 (Signal Transducer And Activator Of Transcription 4)
    |
    Zolinza (vorinostat) • Jingzhuda (entinostat)
    29d
    Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma (clinicaltrials.gov)
    P1/2, N=83, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date • Combination therapy • Metastases
    |
    CD20 (Membrane Spanning 4-Domains A1)
    |
    CD20 expression
    |
    Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • Zolinza (vorinostat) • Mabtas (rituximab biosimilar)
    29d
    SWOG-S1117: Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia (clinicaltrials.gov)
    P2, N=282, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date • Combination therapy
    |
    lenalidomide • azacitidine • Zolinza (vorinostat)
    1m
    Vorinostat for Graft vs Host Disease Prevention in Children, Adolescents and Young Adults Undergoing Allogeneic Blood and Marrow Transplantation (clinicaltrials.gov)
    P1/2, N=49, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Aug 2024 --> Jun 2026 | Trial primary completion date: Aug 2024 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
    |
    cyclophosphamide • Zolinza (vorinostat)
    2ms
    Discovery of novel benzimidazole derivatives as potent HDACs inhibitors against leukemia with (Thio)Hydantoin as zinc-binding moiety: Design, synthesis, enzyme inhibition, and cellular mechanistic study. (PubMed, Bioorg Chem)
    Furthermore, docking study exposed the ability of title compounds to chelate Zn2+ located within HDAC6 active site. As well, in-silico evaluation of physicochemical properties showed that target compounds are promising candidates in terms of pharmacokinetic aspects.
    Journal
    |
    HDAC1 (Histone Deacetylase 1)
    |
    Zolinza (vorinostat)
    2ms
    Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma (clinicaltrials.gov)
    P1, N=18, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date • Metastases
    |
    azacitidine • Zolinza (vorinostat)
    2ms
    Design, Synthesis, and Structure-Activity Relationship of Novel Pyridazinone-Based PARP7/HDACs Dual Inhibitors for Elucidating the Relationship between Antitumor Immunity and HDACs Inhibition. (PubMed, J Med Chem)
    Histone deacetylases (HDACs) inhibitors such as vorinostat (SAHA) has been used to treat hematologic malignancies (rather than solid tumors) and have been found to suppress the JAK/STAT, a critical signal pathway for antitumor immunity, while PARP7 inhibitor RBN-2397 could activate the type I interferons (IFN-I) pathway, facilitating downstream effects such as STAT1 phosphorylation and immune activation. Compound 9l was identified as a potent and balanced dual inhibitor for the first time, exhibiting excellent antitumor capabilities both in vitro and in vivo. This suggests that 9l can be used as a valuable tool molecule for investigating the relationship between anticancer immunity and HDAC inhibition.
    Journal
    |
    TIPARP (TCDD Inducible Poly(ADP-Ribose) Polymerase)
    |
    Zolinza (vorinostat) • atamparib (RBN-2397)
    2ms
    Changes in chromatin accessibility and transcriptional landscape induced by HDAC inhibitors in TP53 mutated patient-derived colon cancer organoids. (PubMed, Biomed Pharmacother)
    In summary, our exploratory study indicates a mechanism of action for SAHA and demonstrate the low efficacy of NKL54 as a single agent for apoptosis induction, using two PDOs. These observations need to be validated in a larger cohort of PDOs.
    Journal
    |
    TP53 (Tumor protein P53) • BCL2L1 (BCL2-like 1)
    |
    TP53 mutation
    |
    Zolinza (vorinostat)
    2ms
    Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)
    P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual
    Trial termination
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • Sutent (sunitinib) • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide capsule) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical
    2ms
    Vorinostat for Graft vs Host Disease Prevention in Children, Adolescents and Young Adults Undergoing Allogeneic Blood and Marrow Transplantation (clinicaltrials.gov)
    P1/2, N=49, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Feb 2024 --> Aug 2024 | Trial primary completion date: Feb 2024 --> Aug 2024
    Trial completion date • Trial primary completion date
    |
    HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
    |
    cyclophosphamide • Zolinza (vorinostat)
    2ms
    Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells. (PubMed, World J Gastrointest Oncol)
    Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells. It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC. Nevertheless, it is still necessary to determine the specific targets of the ZNF710 TF.
    Journal
    |
    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • MIR93 (MicroRNA 93)
    |
    Mekinist (trametinib) • cisplatin • dasatinib • gemcitabine • 5-fluorouracil • Zolinza (vorinostat)
    2ms
    Natural killer cell-based signature: Prognostic analysis in head and neck squamous cell carcinoma. (PubMed, J Gene Med)
    The present study reveals the significance of NK cells in HNSC and their potential as prognostic biomarkers. The CFKZ score offers a promising approach for predicting patient outcomes and guiding personalized treatment decisions in HNSC. These findings contribute to our understanding of HNSC immunobiology and hold implications for precision medicine in HNSC management.
    Journal • IO biomarker
    |
    KIR3DL2 (Killer Cell Immunoglobulin Like Receptor Three Ig Domains And Long Cytoplasmic Tail 2) • FCRL1 (Fc Receptor Like 1)
    |
    methotrexate • Inlyta (axitinib) • sirolimus • Zolinza (vorinostat)
    2ms
    Ph1 Study of FT538 Alone and With Vorinostat for Persistent Low-Level HIV Viremia (clinicaltrials.gov)
    P1, N=0, Withdrawn, Masonic Cancer Center, University of Minnesota | N=34 --> 0
    Enrollment change
    |
    CD4 (CD4 Molecule)
    |
    Zolinza (vorinostat) • FT538
    2ms
    Discovery of novel anticancer flavonoids as potential HDAC2 inhibitors: virtual screening approach based on molecular docking, DFT and molecular dynamics simulations studies. (PubMed, 3 Biotech)
    Eleven out of 329 selected flavonoids were screened based on molecular docking studies, as they have higher binding affinities than the standard drugs vorinostat and panobinostat. Further experimental validation is needed to understand the selectivity of flavonoids as HDAC2 inhibitors. The online version contains supplementary material available at 10.1007/s13205-023-03912-5.
    Journal
    |
    HDAC2 (Histone deacetylase 2)
    |
    Zolinza (vorinostat) • Farydak (panobinostat)
    2ms
    Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma (clinicaltrials.gov)
    P2/3, N=101, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial primary completion date: Sep 2016 --> Jun 2023
    Trial completion • Trial completion date • Trial primary completion date • Combination therapy
    |
    Avastin (bevacizumab) • temozolomide • Zolinza (vorinostat) • Vegzelma (bevacizumab-adcd) • Avzivi (bevacizumab-tnjn)
    2ms
    M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells. (PubMed, Cancer Biol Ther)
    DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels...In conclusion, DIRAS1 exerts a significant anti-oncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer.
    Journal
    |
    ALKBH5 (AlkB Homolog 5, RNA Demethylase) • METTL14 (Methyltransferase 14) • METTL3 (Methyltransferase Like 3)
    |
    FTO expression
    |
    azacitidine • Zolinza (vorinostat)
    3ms
    PEVOsq: Efficacy of Immunotherapy Plus a Drug in Patients With Progressive Advanced Mucosal Cancer of Different Locations (clinicaltrials.gov)
    P2, N=112, Active, not recruiting, UNICANCER | Trial completion date: Oct 2024 --> Jan 2025
    Trial completion date • Pan tumor • Metastases
    |
    Keytruda (pembrolizumab) • Zolinza (vorinostat)
    3ms
    Pembrolizumab and Vorinostat in Patients With Relapsed or Refractory DLBCL, FCL or HL. (clinicaltrials.gov)
    P1, N=52, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Jun 2023
    Trial completion date • Trial primary completion date
    |
    Keytruda (pembrolizumab) • Zolinza (vorinostat)
    3ms
    Pembro and Vorinostat for Patients With Stage IV Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P1/2, N=124, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2024 --> Jan 2025
    Trial completion date • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    Keytruda (pembrolizumab) • Zolinza (vorinostat)
    3ms
    Vorinostat and Temsirolimus With or Without Radiation Therapy in Treating Younger Patients With Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov)
    P1, N=18, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024
    Trial completion date • Trial primary completion date
    |
    Torisel (temsirolimus) • Zolinza (vorinostat)
    3ms
    Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer (clinicaltrials.gov)
    P2, N=68, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2024 --> Feb 2025
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    ER positive • HER-2 negative • PGR negative
    |
    carboplatin • albumin-bound paclitaxel • Zolinza (vorinostat)
    3ms
    Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation With Histone Deacetylase Inhibitors (clinicaltrials.gov)
    P2, N=31, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting --> Completed | Trial completion date: Oct 2023 --> Jul 2023
    Trial completion • Trial completion date • Epigenetic controller
    |
    CD4 (CD4 Molecule)
    |
    tamoxifen • Zolinza (vorinostat)
    3ms
    Chemical Epigenetic Regulation Secondary Metabolites Derived from Aspergillus sydowii DL1045 with Inhibitory Activities for Protein Tyrosine Phosphatases. (PubMed, Molecules)
    In this study, a histone deacetylase inhibitor called suberoylanilide hydroxamic acid (SAHA) was added to a culture of marine fungi (Aspergillus sydowii DL1045) to identify potential drug candidates related to PTP inhibition...Research has demonstrated that CER positively impacts changes in the secondary metabolic patterns of A. sydowii DL1045. The compounds produced through this approach will provide valuable insights for the creation and advancement of novel drug candidates related to PTP inhibition.
    Journal
    |
    PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2)
    |
    Zolinza (vorinostat)
    3ms
    GZ17-6.02 interacts with bexarotene to kill mycosis fungoides cells. (PubMed, Oncotarget)
    Inhibition of autophagy and knock down of death-mediators downstream of the mitochondrion, AIF and caspase 3, almost abolished tumor cell killing. Hence in MF cells, GZ17-6.02 is a multi-factorial killer, utilizing ER stress, macroautophagy, death receptor signaling and directly causing mitochondrial dysfunction.
    Journal
    |
    MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • FAS (Fas cell surface death receptor) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1) • BECN1 (Beclin 1)
    |
    MCL1 expression
    |
    Zolinza (vorinostat) • GZ17-6.02 • Targretin oral (bexarotene oral)
    3ms
    Re-expression of epigenetically silenced PTPRR by histone acetylation sensitizes RAS-mutant lung adenocarcinoma to SHP2 inhibition. (PubMed, Cell Mol Life Sci)
    The combination of the HDAC inhibitor SAHA and SHP2 inhibitor SHP099 suppressed the progression of lung cancer markedly in vitro and in vivo. Therefore, we revealed the epigenetic silencing mechanism of PTPRR and demonstrated that combination therapy targeting HDAC and SHP2 might represent a novel strategy to treat RAS-mutant lung cancer.
    Journal • Epigenetic controller
    |
    ATP6AP2 (ATPase H+ Transporting Accessory Protein 2)
    |
    RAS mutation
    |
    Zolinza (vorinostat) • SHP099
    3ms
    Multitargeting HDAC Inhibitors Containing a RAS/RAF Protein Interfering Unit. (PubMed, J Med Chem)
    Among them, two representative compounds, XSJ-7 and XSJ-10, not only showed stronger antiproliferative activity against many types of cancer cells including solid tumor cells but also presented more potent inhibition on different subtypes of HDAC than suberoylanilide hydroxamic acid (SAHA). Significantly, XSJ-10 presented moderate pharmacokinetic behaviors and showed stronger antitumor activity than oxaliplatin, SAHA, and rigosertib in the HT-29 xenograft mouse models without significant systemic toxicity. Research on the anticancer mechanism of XSJ-10 revealed that it can effectively induce the apoptosis of cancer cells and suppress the tumor by strongly inhibiting the RAS-RAF-MEK-ERK signaling pathway and the acetylation level of HDAC3.
    Journal
    |
    HDAC3 (Histone Deacetylase 3)
    |
    oxaliplatin • Zolinza (vorinostat) • Estybon (rigosertib)
    4ms
    Vorinostat and Combination Chemotherapy Before Donor Stem Cell Transplantation for the Treatment of Relapsed Aggressive B-cell or T-cell Non-Hodgkin Lymphoma (clinicaltrials.gov)
    P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=30 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
    |
    gemcitabine • Rituxan (rituximab) • cyclophosphamide • Zolinza (vorinostat) • clofarabine • busulfan
    4ms
    Novel combination of imipridones and histone deacetylase inhibitors demonstrate cytotoxic effect through integrated stress response in pediatric solid tumors. (PubMed, Am J Cancer Res)
    ONC201, ONC206, and ONC212 are imipridones showing pro-apoptotic anti-cancer response...Additionally, pediatric solid tumor cells were treated with single-agent therapy with histone deacetylase inhibitors (HDACi) vorinostat, entinostat, and panobinostat, showing cell killing with all 3 HDACi drugs, with panobinostat showing the greatest potency...Our results introduce a novel class of small molecules to treat pediatric solid tumors in a precision medicine framework. Use of impridones in pediatric oncology is novel and shows promising pre-clinical efficacy in pediatric solid tumors, including in combination with HDAC inhibitors.
    Journal • Epigenetic controller
    |
    ATF4 (Activating Transcription Factor 4)
    |
    Zolinza (vorinostat) • Farydak (panobinostat) • Jingzhuda (entinostat) • dordaviprone (ONC201) • ONC212 • ONC206
    4ms
    TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II (clinicaltrials.gov)
    P1/2, N=90, Recruiting, Tanja Andrea Gruber | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    CD19 positive
    |
    bortezomib • Blincyto (blinatumomab) • Zolinza (vorinostat) • mitoxantrone • ziftomenib (KO-539) • mercaptopurine
    4ms
    The methyltransferases METTL7A and METTL7B confer resistance to thiol-based histone deacetylase inhibitors. (PubMed, Mol Cancer Ther)
    To identify alternative mechanisms of resistance to romidepsin, we selected MCF-7 breast cancer cells with romidepsin in the presence of the P-gp inhibitor verapamil to reduce the likelihood of P-gp-mediated resistance. The resulting cell line, MCF-7 DpVp300, does not express P-gp and was found to be selectively resistant to romidepsin but not to other HDACis such as belinostat, panobinostat, or vorinostat. RNA sequencing analysis revealed upregulation of the mRNA coding for the putative methyltransferase, METTL7A, whose paralog, METTL7B, was previously shown to methylate thiol groups on hydrogen sulfide and captopril...We demonstrate that expression of METTL7A or METTL7B confers resistance to thiol-based HDACis and that both enzymes are capable of methylating thiol-containing HDACis. We thus propose that METTL7A and METTL7B confer resistance to thiol-based HDACis by methylating and inactivating the zinc-binding thiol.
    Journal • Epigenetic controller
    |
    ABCB1 (ATP Binding Cassette Subfamily B Member 1)
    |
    ABCB1 expression
    |
    Zolinza (vorinostat) • Farydak (panobinostat) • Istodax (romidepsin) • Beleodaq (belinostat) • captopril