^
    3ms
    ZEB1 promotes chemo-immune resistance in pancreatic cancer models by downregulating chromatin acetylation of CXCL16. (PubMed, J Clin Invest)
    ZEB1 knockdown synergized with gemcitabine and anti-PD1 therapy, markedly suppressed PC growth, and prolonged survival in vivo. Importantly, the epigenetic inhibitor Mocetinostat (targeting ZEB1) potentiated chemoimmunotherapy efficacy, including anti-PD1 and CAR-T therapies, in patient-derived organoids, xenografts, and orthotopic models. Our study unveils ZEB1 as a master epigenetic regulator of chemoimmunotherapy resistance and proposes its targeting as a transformative strategy for PC treatment.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • SPP1 (Secreted Phosphoprotein 1) • GZMA (Granzyme A) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • CXCL16 (C-X-C Motif Chemokine Ligand 16)
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    gemcitabine • mocetinostat (MGCD0103)
    4ms
    Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer. (clinicaltrials.gov)
    P1, N=28, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2025 --> Jul 2026
    Trial completion date • Trial primary completion date
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    Keytruda (pembrolizumab) • mocetinostat (MGCD0103) • guadecitabine (SGI-110)
    5ms
    Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma (clinicaltrials.gov)
    P1, N=38, Active, not recruiting, Jonsson Comprehensive Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2025 --> May 2026
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    vinorelbine tartrate • vinblastine • mocetinostat (MGCD0103)
    7ms
    Design, synthesis, and biological evaluation of N-(2-amino-phenyl)-5-(4-aryl- pyrimidin-2-yl) amino)-1H-indole-2-carboxamide derivatives as novel inhibitors of CDK9 and class I HDACs for cancer treatment. (PubMed, Bioorg Chem)
    The cellular assays revealed that 13ea induced mitochondria-related apoptosis and G2/M phase arrest in cancer cells, showing superior activities compared to those of AZD-5438 (a CDK9 inhibitor) and Mocetinostat (an inhibitor of class I HDACs). Notably, the in vivo assay demonstrated that 13ea (30 mg/kg) exhibited significant inhibition on MDA-MB-231 xenograft tumor growth, with a tumor shrinkage rate of 76.83 %. In summary, we have identified 13ea as a novel CDK9/HDAC inhibitor with excellent anticancer activity in vitro and in vivo.
    Journal
    |
    CDK9 (Cyclin Dependent Kinase 9) • HDAC1 (Histone Deacetylase 1) • HDAC3 (Histone Deacetylase 3)
    |
    mocetinostat (MGCD0103)
    9ms
    Proteomic analysis reveals chromatin remodeling as a potential therapeutical target in neuroblastoma. (PubMed, J Transl Med)
    Mocetinostat and clofarabine offer valuable insights for the development of novel targeted therapies in neuroblastoma.
    Journal
    |
    ARID1A (AT-rich interaction domain 1A) • SF3B1 (Splicing Factor 3b Subunit 1) • PBRM1 (Polybromo 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ARID1B (AT-Rich Interaction Domain 1B) • TP53BP1 (Tumor Protein P53 Binding Protein 1) • ALYREF (Aly/REF Export Factor) • BRD2 (Bromodomain Containing 2) • BRD3 (Bromodomain Containing 3) • SMARCA5 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 5)
    |
    clofarabine • mocetinostat (MGCD0103)
    12ms
    HDAC Inhibitors Can Enhance Radiosensitivity of Head and Neck Cancer Cells Through Suppressing DNA Repair. (PubMed, Cancers (Basel))
    We identified that histone deacetylases (HDACs) were prominent candidates, and subsequently identified that the HDAC inhibitors mocetinostat and pracinostat, as well as the combined HDAC-epidermal growth factor receptor inhibitor CUDC-101, were effective at radiosensitising cell models of HNSCC (FaDu, A253, UMSCC11b) through their impact on both spheroid growth and clonogenic survival assays. We also demonstrated that this combinatorial strategy leads to inhibition of the repair of DNA double-strand breaks through the neutral comet assay and γH2AX foci analysis using immunofluorescence microscopy, providing a mechanism of action through which HDAC inhibition functions in HNSCC radiosensitisation. We believe that this approach should be further investigated in preclinical models, in order to realise the full therapeutic potential of HDAC inhibition for the radiosensitisation of HNSCC, eventually leading to improved patient treatment efficacy and outcomes.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
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    pracinostat (SB939) • mocetinostat (MGCD0103) • CUDC-101
    1year
    Sacubitril/Valsartan in PriMAry preventIoN of the cardiotoxicity of systematic breaST canceR trEAtMent Sakubitryl/walsartan w zapobieganiu uszkodzeniu serca w trakcie leczenia chorych na raka piersi (clinicaltrialsregister.eu)
    P4, N=480, Ongoing, Śląskie Centrum Chorób Serca
    New P4 trial
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    PGR (Progesterone receptor)
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    mocetinostat (MGCD0103)
    over1year
    Entinostat as a combinatorial therapeutic for rhabdomyosarcoma. (PubMed, Sci Rep)
    We identified single agent, additive or synergistic relationships between relapse-specific chemotherapies and clinically relevant drug exposures of entinostat in three PAX3::FOXO1+ ARMS mouse models. This preclinical data provides further rationale for clinical investigation of entinostat, already known to be well tolerated in a pediatric phase I clinical trial (ADVL1513).
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FOXO1 (Forkhead box O1) • MIR27A (MicroRNA 27a) • HDAC3 (Histone Deacetylase 3) • PAX3 (Paired Box 3)
    |
    Jingzhuda (entinostat) • mocetinostat (MGCD0103)
    over1year
    Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer. (clinicaltrials.gov)
    P1, N=28, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    Keytruda (pembrolizumab) • mocetinostat (MGCD0103) • guadecitabine (SGI-110)
    over1year
    Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma (clinicaltrials.gov)
    P1, N=38, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2024 --> May 2025
    Trial completion date • Trial primary completion date • Combination therapy
    |
    vinorelbine tartrate • vinblastine • mocetinostat (MGCD0103)
    over1year
    MRTX-500: Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=161, Terminated, Mirati Therapeutics Inc. | Completed --> Terminated; This study was terminated as a result of Sponsor portfolio reprioritization.
    Trial termination • Combination therapy • Metastases
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    Opdivo (nivolumab) • sitravatinib (MGCD516) • glesatinib (MGCD265) • mocetinostat (MGCD0103)
    over1year
    Study of Mocetinostat in Selected Patients With Mutations of Acetyltransferase Genes in Relapsed and Refractory Diffuse Large B-Cell Lymphoma and Follicular Lymphoma (clinicaltrials.gov)
    P1/2, N=7, Terminated, Memorial Sloan Kettering Cancer Center | Phase classification: P2 --> P1/2
    Phase classification
    |
    CREBBP (CREB binding protein)
    |
    CREBBP mutation • EP300 mutation
    |
    mocetinostat (MGCD0103)