ArticleCancer science2017
Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
83 citing papers in PubMed, 139 citations in OpenAlex.
- Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study.The Lancet. Oncology · 2024Trial
- Structural characteristics and SARs of EZH2 inhibitors.Molecular diversity · 2026Review
- Enhancer of Zeste Homolog 2 (EZH2): From Glioblastoma Biology to Potential Epigenetic Therapy.International journal of molecular sciences · 2026Review
- Physiologically Based Pharmacokinetic Modeling of Valemetostat to Inform Dose Recommendations When Coadministered With CYP3A/P-gp Modulators.Clinical and translational science · 2025Article
- Dual EZH1/2 inhibition enhances DNMT inhibitor efficacy in colon cancer through targeting H3K27me1.bioRxiv : the preprint server for biology · 2025Article
- Impact of Novel Agents on Allogeneic Hematopoietic Cell Transplantation in Patients with T-Cell Lymphomas.Cells · 2025Review
- EZH1 deficiency promotes ferroptosis resistance by activating NRF2 in sepsis-associated liver injury.Clinical epigenetics · 2025Article
- Toll-Interacting Protein Down-Regulation by Cigarette Smoke Exposure Impairs Human Lung Defense against Influenza A Virus Infection.The American journal of pathology · 2025Article
- Treating human cancer by targeting EZH2.Genes & diseases · 2025Review
- Dual targeting of EZH2 and EZH1 drives exit of leukemia stem cells from quiescence and potentiates chemotherapy in acute myeloid leukemia.Blood cancer journal · 2025Article
- Pharmacokinetics, metabolism, and excretion of [Cancer chemotherapy and pharmacology · 2025Article
- Reduced EZH1/2 expression in imipridone-treated cells correlates with synergy following combinations with EZH1/2 or HDAC inhibitors in diffuse glioma and other tumors.American journal of cancer research · 2025Article
- Enhancer of zeste homolog 1/2 dual inhibitor valemetostat outperforms enhancer of zeste homolog 2-selective inhibitors in reactivating latent HIV-1 reservoirsFrontiers in microbiology · 2025Article
- Molecular insight into histone methylation as a novel target for oral squamous cell carcinoma: future hope in personalised medicine.Journal of Cancer · 2025Review
- Valemetostat monotherapy in patients with relapsed or refractory non-Hodgkin lymphoma: a first-in-human, multicentre, open-label, single-arm, phase 1 study.The Lancet. Oncology · 2024Article
- Hypermethylation of CDKN2A CpG island drives resistance to PRC2 inhibitors in SWI/SNF loss-of-function tumors.Cell death & disease · 2024Article
- Review
- Circulating tumor cells: from new biological insights to clinical practice.Signal transduction and targeted therapy · 2024Review
- Chromatin remodellers as therapeutic targets.Nature reviews. Drug discovery · 2024Review
- Dual-target EZH2 inhibitor: latest advances in medicinal chemistry.Future medicinal chemistry · 2024Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual inhibitors that strongly and selectively inhibited methyltransferase activity of both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo against diffuse large B-cell lymphoma cells harboring gain-of-function mutation in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL-AF9, MLL-AF4, and AML1-ETO. A solid cancer panel assay demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor in vitro and in vivo. No clear correlation was detected between sensitivity to EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at drug levels higher than those used in the antitumor study. Our results indicate the possibility of EZH1/2 dual inhibitors for clinical applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.