ArticleBlood2015
Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.
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Who cites it
159 citing papers in PubMed, 230 citations in OpenAlex.
- Targeting the Epigenetic-Immune Axis in Acute Myeloid Leukemia: Current Advances and Future Directions.Current oncology reports · 2026Review
- Exploiting an epigenetic resistance mechanism to PI3-kinase inhibition in leukemic stem cells.Leukemia · 2026Article
- MLL3 and MLL4 sustain hematopoietic stem cell multipotency by opposing a B-cell default state.Blood · 2026Article
- Unveiling Candidate Markers for Drug Resistance or Synthetic Lethality in Cervical Cancer: Integrative Analysis of Genetic and Pharmacoprofiling.Cancer reports (Hoboken, N.J.) · 2026Article
- A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- Xist RNA dependent and independent mechanisms regulate dynamic X chromosome inactivation in B lymphocytes.Cell reports · 2026Article
- Biological Evaluation of a Novel Compound with Predicted EZH2 and EED Binding Against Human Malignant Melanoma Cells.International journal of molecular sciences · 2026Article
- Epigenetic landscape of the H3K27me3 mark in macrophages transformed by Theileria annulata.Communications biology · 2026Article
- Exploring the role of EZH2 in neuroinflammation: implications for innovative therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Epigenetic regulation of EZH2 by ncRNAs: mechanisms and oncogenic implications.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Targeting dysregulated epigenetic and transcription factor networks inBlood neoplasia · 2026Article
- SKIDA1 sustains MLL::ENL-expressing hematopoietic progenitors during neonatal stages and promotes B-lineage priming.Blood neoplasia · 2026Article
- Therapeutic targeting SPI1 in combination with erastin promotes ferroptosis in ccRCC.Communications biology · 2025Article
- AKR1B1 is Required for Maintaining Acute Leukemia Cell Survival by Epigenetic Silencing of Tumor Suppressor Genes.Biochemical genetics · 2025Article
- Review
- Heritable maintenance of chromatin modifications confers transcriptional memory of interferon-γ signaling.Nature structural & molecular biology · 2025Article
- 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
- Squamocin Suppresses Tumor Growth through Triggering an Endoplasmic Reticulum Stress-Associated Degradation of EZH2/MYC Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- EZH1/EZH2 inhibition enhances adoptive T cell immunotherapy against multiple cancer models.Cancer cell · 2025Article
- The phenylalanine-and-glycine repeats of NUP98 oncofusions form condensates that selectively partition transcriptional coactivators.Molecular cell · 2025Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Enhancer of zeste homolog 2 (EZH2) and related EZH1 control gene expression and promote tumorigenesis via methylating histone H3 at lysine 27 (H3K27). These methyltransferases are ideal therapeutic targets due to their frequent hyperactive mutations and overexpression found in cancer, including hematopoietic malignancies. Here, we characterized a set of small molecules that allow pharmacologic manipulation of EZH2 and EZH1, which include UNC1999, a selective inhibitor of both enzymes, and UNC2400, an inactive analog compound useful for assessment of off-target effect. UNC1999 suppresses global H3K27 trimethylation/dimethylation (H3K27me3/2) and inhibits growth of mixed lineage leukemia (MLL)-rearranged leukemia cells. UNC1999-induced transcriptome alterations overlap those following knockdown of embryonic ectoderm development, a common cofactor of EZH2 and EZH1, demonstrating UNC1999's on-target inhibition. Mechanistically, UNC1999 preferentially affects distal regulatory elements such as enhancers, leading to derepression of polycomb targets including Cdkn2a. Gene derepression correlates with a decrease in H3K27me3 and concurrent gain in H3K27 acetylation. UNC2400 does not induce such effects. Oral administration of UNC1999 prolongs survival of a well-defined murine leukemia model bearing MLL-AF9. Collectively, our study provides the detailed profiling for a set of chemicals to manipulate EZH2 and EZH1 and establishes specific enzymatic inhibition of polycomb repressive complex 2 (PRC2)-EZH2 and PRC2-EZH1 by small-molecule compounds as a novel therapeutics for MLL-rearranged leukemia.
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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.