Cited by 807Epigenetics and DNA MethylationCancer-related gene regulationChromatin Remodeling and Cancer

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells

Knutson, Sarah K, Wigle, Tim J, Warholic, Natalie M, Sneeringer, Christopher J, Allain, Christina J, Klaus, Christine R, Sacks, Joelle D, Raimondi, Alejandra, Majer, Christina R, Song, Jeffrey, Scott, Margaret Porter, Jin, Lei, Smith, Jesse J, Olhava, Edward J, Chesworth, Richard, Moyer, Mikel P, Richon, Victoria M, Copeland, Robert A, Keilhack, Heike, Pollock, Roy M, Kuntz, Kevin W·2012·Nature Chemical Biology

DOI 10.1038/nchembio.1084

Open this paper in CoChat — free account

Abstract

EZH2 catalyzes trimethylation of histone H3 lysine 27 (H3K27). Point mutations of EZH2 at Tyr641 and Ala677 occur in subpopulations of non-Hodgkin's lymphoma, where they drive H3K27 hypertrimethylation. Here we report the discovery of EPZ005687, a potent inhibitor of EZH2 (K(i) of 24 nM). EPZ005687 has greater than 500-fold selectivity against 15 other protein methyltransferases and has 50-fold selectivity against the closely related enzyme EZH1. The compound reduces H3K27 methylation in various lymphoma cells; this translates into apoptotic cell killing in heterozygous Tyr641 or Ala677 mutant cells, with minimal effects on the proliferation of wild-type cells. These data suggest that genetic alteration of EZH2 (for example, mutations at Tyr641 or Ala677) results in a critical dependency on enzymatic activity for proliferation (that is, the equivalent of oncogene addiction), thus portending the clinical use of EZH2 inhibitors for cancers in which EZH2 is genetically altered.

Integrity signals

Registry

Crossref · 10.1038/nchembio.1084

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Kwak, E. L., Bang, Y., Camidge, D. R., Shaw, A. T., Solomon, B., Maki, R. G., Ou, S. I., Dezube, B. J., Janne, P. A., Costa, D. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1006448 · Cited by 4,477
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., & Zhang, Y. (2002) · Science · doi:10.1126/science.1076997 · Cited by 3,775
The polycomb group protein EZH2 is involved in progression of prostate cancer
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., et al. (2002) · Nature · doi:10.1038/nature01075 · Cited by 2,717
An embryonic stem cell–like gene expression signature in poorly differentiated aggressive human tumors
Ben‐Porath, I., Thomson, M., Carey, V. J., Ge, R., Bell, G. W., Regev, A., & Weinberg, R. A. (2008) · Nature Genetics · doi:10.1038/ng.127 · Cited by 2,571
Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin
Morin, R. D., Johnson, N. A., Severson, T., Mungall, A. J. J., An, J., Goya, R., Paul, J. E., Boyle, M., Woolcock, B. W., Kuchenbauer, F. C., et al. (2010) · Nature Genetics · doi:10.1038/ng.518 · Cited by 1,719
EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells
Kleer, C. G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S. A., Ghosh, D., Sewalt, R. G. A. B., Otte, A. P., Hayes, D. F., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1933744100 · Cited by 1,649
Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma
Morin, R. D., Mendez-Lago, M., Mungall, A. J., Goya, R., Mungall, K. L., Corbett, R. D., Johnson, N. A., Severson, T. M., Chiu, R., Field, M., et al. (2011) · Nature · doi:10.1038/nature10351 · Cited by 1,614
Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein
Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., & Reinberg, D. (2002) · Genes & Development · doi:10.1101/gad.1035902 · Cited by 1,596
UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development
Agger, K., Cloos, P. A., Christensen, J. F., Pasini, D., Rose, S., Rappsilber, J., Issaeva, I., Canaani, E., Salcini, A. E., & Helin, K. (2007) · Nature · doi:10.1038/nature06145 · Cited by 1,392

Show all 46 references

Sorted by citations

Items 301–400 of 807

A recurrent endometrial stromal sarcoma harbors the novel fusion JAZF1-BCORL1
Allen, A. J., Ali, S. M., Gowen, K. A., Elvin, J. A., & Pejovic, T. B. (2017) · Gynecologic Oncology Reports · doi:10.1016/j.gore.2017.03.002 · Cited by 52
Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress
Liao, Y., Chen, C.-H., Xiao, T., Avalos, B. D. L. P., Dray, E. V., Cai, C., Gao, S., Shah, N., Zhang, Z., Feit, A. S., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2105898119 · Cited by 52
Role of somatic cancer mutations in human protein lysine methyltransferases
Kudithipudi, S., & Jeltsch, A. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.08.002 · Cited by 55
Polycomb Repressive Complex 2 Silences Human Cytomegalovirus Transcription in Quiescent Infection Models
Abraham, C. G., & Kulesza, C. A. (2013) · Journal of Virology · doi:10.1128/jvi.02420-13 · Cited by 58
Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent cancer
Chen, H.-M., Gao, S., Li, J., Liu, D., Sheng, C., Yao, C., Jiang, W., Wu, J., Chen, S., & Huang, W. (2015) · Oncotarget · doi:10.18632/oncotarget.3790 · Cited by 51
Epigenetic mechanisms regulating the development of hepatocellular carcinoma and their promise for therapeutics
Khan, F. S., Ali, I., Afridi, U. K., Ishtiaq, M., & Mehmood, R. (2016) · Hepatology International · doi:10.1007/s12072-016-9743-4 · Cited by 52
KDM5 inhibition offers a novel therapeutic strategy for the treatment of KMT2D mutant lymphomas
Heward, J. A., Koniali, L., D’Avola, A., Close, K., Yeomans, A., Philpott, M., Dunford, J. E., Rahim, T., Seraihi, A. A., Wang, J., et al. (2021) · Blood · doi:10.1182/blood.2020008743 · Cited by 53
Epigenetic targets and drug discovery
Liu, Y., Liu, K., Su, Q., Xu, C., & Min, J. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.03.007 · Cited by 51
A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation
Ott, H. M., Graves, A. P., Pappalardi, M. B., Huddleston, M. J., Halsey, W. S., Hughes, A. M., Groy, A., Dul, E., Jiang, Y., Bai, Y., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0876 · Cited by 51
The histone methyltransferase EZH2 as a druggable target in SHH medulloblastoma cancer stem cells
Miele, E., Valente, S., Alfano, V., Silvano, M., Mellini, P., Borovika, D., Marrocco, B., Pò, A., Besharat, Z. M., Catanzaro, G., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.19782 · Cited by 49
Epigenetic small molecule modulators of histone and DNA methylation
Hauser, A., Robaa, D., & Jung, M. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.03.003 · Cited by 50
EZH2-mediated Puma gene repression regulates non-small cell lung cancer cell proliferation and cisplatin-induced apoptosis
Liu, H., Li, W., Yu, X., Gao, F., Duan, Z., Ma, X., Tan, S., Yuan, Y., Liu, L., Wang, J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10841 · Cited by 50
Natural compound-derived epigenetic regulators targeting epigenetic readers, writers and erasers
Yang, Y., Kim, H., Li, W., & Kong, A. T. (2015) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026615666150826114359 · Cited by 52
EZH2 inhibitors: a patent review (2014-2016)
Stazi, G., Zwergel, C., Mai, A., & Valente, S. (2017) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2017.1316976 · Cited by 49
EZH2 inhibition in ARID1A mutated clear cell and endometrioid ovarian and endometrioid endometrial cancers
Alldredge, J. K., & Eskander, R. N. (2017) · Gynecologic Oncology Research and Practice · doi:10.1186/s40661-017-0052-y · Cited by 52
Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer
Zhao, C., Zeng, C., Ye, S., Dai, X., He, Q., Yang, B., & Zhu, H. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.12.010 · Cited by 49
The mechanisms of action of chromatin remodelers and implications in development and disease
Sahu, R. K., Singh, S., & Tomar, R. S. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114200 · Cited by 50
Open Access Chemical Probes for Epigenetic Targets
Brown, P. J., & Müller, S. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.127 · Cited by 48
Prevalence of targetable oncogenic mutations and genomic alterations in Epstein–Barr virus-associated diffuse large B-cell lymphoma of the elderly
Gebauer, N., Gebauer, J., Hardel, T. T., Bernard, V., Biersack, H., Lehnert, H., Rades, D., Feller, A. C., & Thorns, C. (2014) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2014.944522 · Cited by 48
Epigenetic Programing of B-Cell Lymphoma by BCL6 and Its Genetic Deregulation
Yang, H., & Green, M. R. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00272 · Cited by 48
Lysine methyltransferase inhibitors: where we are now
Feoli, A., Viviano, M., Cipriano, A., Milite, C., Castellano, S., & Sbardella, G. (2021) · RSC Chemical Biology · doi:10.1039/d1cb00196e · Cited by 50
SWI/SNF Complexes in Ovarian Cancer: Mechanistic Insights and Therapeutic Implications
Fukumoto, T., Magno, E., & Zhang, R. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-0368 · Cited by 47
Epigenetic reprogramming by tumor-derived EZH2 gain-of-function mutations promotes aggressive 3D cell morphologies and enhances melanoma tumor growth
Barsotti, A. M., Ryskin, M., Zhong, W., Zhang, W., Giannakou, A., Loreth, C., Diesl, V., Follettie, M. T., Golas, J., Lee, M., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.2758 · Cited by 46
Histone Deacetylase and Enhancer of Zeste Homologue 2 Dual Inhibitors Presenting a Synergistic Effect for the Treatment of Hematological Malignancies
Lu, D., Wang, C., Qu, L., Yin, F., Li, S., Luo, H., Zhang, Y., Liu, X., Chen, X., Luo, Z., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00673 · Cited by 46
A cryptic transactivation domain of EZH2 binds AR and AR’s splice variant, promoting oncogene activation and tumorous transformation
Wang, J., Park, K., Yu, X., Gong, W., Earp, H. S., Wang, G. G., Jin, J. J., & Cai, L. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac861 · Cited by 47
A key role for EZH2 in epigenetic silencing of HOX genes in mantle cell lymphoma
Kanduri, M., Sander, B., Ntoufa, S., Papakonstantinou, N., Sutton, L., Σταματόπουλος, Κ., Kanduri, C., & Rosenquist, R. (2013) · Epigenetics · doi:10.4161/epi.26546 · Cited by 46
Small-molecular modulators of cancer-associated epigenetic mechanisms
Itoh, Y., Suzuki, T., & Miyata, N. (2013) · Molecular BioSystems · doi:10.1039/c3mb25410k · Cited by 46
Epigenetic modification in chromatin machinery and its deregulation in pediatric brain tumors: Insight into epigenetic therapies
Maury, E., & Hashizume, R. (2017) · Epigenetics · doi:10.1080/15592294.2016.1278095 · Cited by 50
Targeting epigenetics in sarcomas through EZH2 inhibition
Italiano, A. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00868-4 · Cited by 46
Epigenetic therapies by targeting aberrant histone methylome in AML: molecular mechanisms, current preclinical and clinical development
Tsai, C. T., & So, C. W. E. (2016) · Oncogene · doi:10.1038/onc.2016.315 · Cited by 49
EZH2 inhibitors transcriptionally upregulate cytotoxic autophagy and cytoprotective unfolded protein response in human colorectal cancer cells.
Hsieh, Y., Lo, H.-L., & Yang, P. (2016) · Europe PMC (PubMed Central) · Cited by 45
Polycomb Repressor Complex 2 in Genomic Instability and Cancer
Veneti, Z., Gkouskou, K. K., & Eliopoulos, A. G. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081657 · Cited by 49
Induction of senescence-associated secretory phenotype underlies the therapeutic efficacy of PRC2 inhibition in cancer
Chu, L., Qu, Y.-X., An, Y., Hou, L., Li, J., Li, W., Fan, G., Song, B., Li, E., Zhang, L., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04601-6 · Cited by 47
Deregulated JAK/STAT signalling in lymphomagenesis, and its implications for the development of new targeted therapies
Scott, L. M., & Gandhi, M. K. (2015) · Blood Reviews · doi:10.1016/j.blre.2015.06.002 · Cited by 47
Discovery of IHMT-337 as a potent irreversible EZH2 inhibitor targeting CDK4 transcription for malignancies
Mei, H., Wu, H., Yang, J. C., Zhou, B., Wang, A., Hu, C., Qi, S., Jiang, Z., Zou, F., Wang, B., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01240-3 · Cited by 45
Design, Synthesis, and Biological Evaluation of a Potent Dual EZH2–BRD4 Inhibitor for the Treatment of Some Solid Tumors
Huang, N., Liao, P. S., Zuo, Y., Zhang, L., & Jiang, R. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01607 · Cited by 45
Epigenetic regulation of HIV-1 latency: focus on polycomb group (PcG) proteins
Khan, S., Iqbal, M., Tariq, M., Baig, S. M., & Abbas, W. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0441-z · Cited by 46
Epigenetic regulation of prostate cancer: the theories and the clinical implications
Xu, K., & Liao, Y. (2018) · Asian Journal of Andrology · doi:10.4103/aja.aja_53_18 · Cited by 45
Advances and perspectives of proteolysis targeting chimeras (PROTACs) in drug discovery
Xi, J., Zhang, R., Chen, K., Yao, L., Li, M., Jiang, R., Li, X., & Fan, L. (2022) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.105848 · Cited by 45
Effects of Novel ncRNA Molecules, p15‐piRNAs, on the Methylation of DNA and Histone H3 of the CDKN2B Promoter Region in U937 Cells
Wu, D., Fu, H., Zhou, H., Su, J., Zhang, F., & Shen, J. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25199 · Cited by 43
Epigenetic modifications as new targets for liver disease therapies
Zeybel, M., Mann, D. A., & Mann, J. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.05.039 · Cited by 44
The methylation landscape of tumour metastasis
Cock-Rada, A. M., & Weitzman, J. B. (2012) · Biology of the Cell · doi:10.1111/boc.201200029 · Cited by 45
Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma
Dupéré-Richer, D., & Licht, J. D. (2017) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000358 · Cited by 43
Structure-Guided Development of Small-Molecule PRC2 Inhibitors Targeting EZH2–EED Interaction
Du, D., Xu, D., Zhu, L., Stazi, G., Zwergel, C., Liu, Y., Luo, Z., Li, Y., Zhang, Y., Zhu, K., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c02261 · Cited by 45
Emerging role of G9a in cancer stemness and promises as a therapeutic target
Haebe, J. R., Bergin, C. J., Sandouka, T., & Benoit, Y. D. (2021) · Oncogenesis · doi:10.1038/s41389-021-00370-7 · Cited by 43
Select EZH2 inhibitors enhance viral mimicry effects of DNMT inhibition through a mechanism involving NFAT:AP-1 signaling
Chomiak, A. A., Tiedemann, R. L., Liu, Y., Kong, X., Cui, Y., Wiseman, A. K., Thurlow, K. E., Cornett, E. M., Topper, M. J., Baylin, S. B., et al. (2024) · Science Advances · doi:10.1126/sciadv.adk4423 · Cited by 44
Deciphering HIC1 control pathways to reveal new avenues in cancer therapeutics
Rood, B. R., & Leprince, D. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.788152 · Cited by 42
The Methylation Status of the Epigenome: Its Emerging Role in the Regulation of Tumor Angiogenesis and Tumor Growth, and Potential for Drug Targeting
Pirola, L., Ciesielski, O., & Balcerczyk, A. (2018) · Cancers · doi:10.3390/cancers10080268 · Cited by 43
Preclinical pharmacokinetic studies of 3-deazaneplanocin A, a potent epigenetic anticancer agent, and its human pharmacokinetic prediction using GastroPlus™
Sun, F., Lee, L., Zhang, Z., Wang, X., Yu, Q., Duan, X., & Chan, E. (2015) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2015.06.021 · Cited by 42
EZH2 and NF-κB: A context-dependent crosstalk and transcriptional regulation in cancer
Kaur, P., Verma, S., Kushwaha, P. P., & Gupta, S. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216143 · Cited by 42
Polycomb genes, miRNA, and their deregulation in B-cell malignancies
Wang, G. G., Konze, K. D., & Tao, J. (2015) · Blood · doi:10.1182/blood-2014-10-606822 · Cited by 42
Histone Methyltransferase and Histone Methylation in Inflammatory T-Cell Responses
He, S., Tong, Q., Bishop, D. K., & Zhang, Y. (2013) · Immunotherapy · doi:10.2217/imt.13.101 · Cited by 41
Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression
Xu, H., Xu, K., He, H. H., Zang, C., Chen, C.-H., Chen, Y., Qin, Q., Wang, S., Wang, C., Hu, S. S., et al. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0313 · Cited by 39
Systematic literature review reveals suboptimal use of chemical probes in cell-based biomedical research
Sterling, J., Baker, J. R., McCluskey, A., & Munoz, L. (2023) · Nature Communications · doi:10.1038/s41467-023-38952-1 · Cited by 40
Inhibitors of Emerging Epigenetic Targets for Cancer Therapy: a Patent Review (2010–2014)
Tanaka, M., Roberts, J. M., Qi, J., & Bradner, J. E. (2015) · Pharmaceutical Patent Analyst · doi:10.4155/ppa.15.16 · Cited by 41
Targeting Chromatin Remodeling in Inflammation and Fibrosis
Yang, J., Tian, B., & Brasier, A. R. (2016) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2016.11.001 · Cited by 40
Bioinformatics analysis of thousands of TCGA tumors to determine the involvement of epigenetic regulators in human cancer
Gnad, F., Doll, S., Manning, G., Arnott, D. P., & Zhang, Z. (2015) · BMC Genomics · doi:10.1186/1471-2164-16-s8-s5 · Cited by 38
Synthetic trimethyllysine receptors that bind histone 3, trimethyllysine 27 (H3K27me3) and disrupt its interaction with the epigenetic reader protein CBX7
Tabet, S., Douglas, S. F., Daze, K. D., Garnett, G. A. E., Allen, K. J. H., Abrioux, E. M. M., Quon, T. T. H., Wulff, J. E., & Hof, F. A. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.09.024 · Cited by 40
Histone lysine methyltransferases as anti-cancer targets for drug discovery
Liu, Q., & Wang, M. (2016) · Acta Pharmacologica Sinica · doi:10.1038/aps.2016.64 · Cited by 39
Follicular lymphoma, a B cell malignancy addicted to epigenetic mutations
Korfi, K., Ali, S. E., Heward, J. A., & Fitzgibbon, J. (2017) · Epigenetics · doi:10.1080/15592294.2017.1282587 · Cited by 40
Discovery of EBI-2511: A Highly Potent and Orally Active EZH2 Inhibitor for the Treatment of Non-Hodgkin’s Lymphoma
Lu, B., Shen, X., Zhang, L. J., Liu, D., Zhang, C., Cao, J., Shen, R., Zhang, J., Wang, D., Wan, H., et al. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.7b00437 · Cited by 39
Silencing of developmental genes by H3K27me3 and DNA methylation reflects the discrepant plasticity of embryonic and extraembryonic lineages
Yang, X., Hu, B., Hou, Y., Qiao, Y., Wang, R., Chen, Y., Qian, Y., Feng, S., Chen, J., Liu, C., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0010-1 · Cited by 39
Pathogenesis and biomarkers of natural killer T cell lymphoma (NKTL)
Somasundaram, N., Lim, J. Q., Ong, C. K., & Lim, S. T. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0717-6 · Cited by 39
Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer
Yamada, L., Saito, M., Min, A. K. T., Saito, K., Ashizawa, M., Kase, K., Nakajima, S., Onozawa, H., Okayama, H., Endo, H., et al. (2020) · Gastric Cancer · doi:10.1007/s10120-020-01094-0 · Cited by 39
The Oncogenic Polycomb Histone Methyltransferase EZH2Methylates Lysine 120 on Histone H2B and Competes Ubiquitination
Kogure, M., Takawa, M., Saloura, V., Sone, K., Piao, L., Ueda, K., Ibrahim, R., Tsunoda, T., Sugiyama, M., Atomi, Y., et al. (2013) · Neoplasia · doi:10.1593/neo.131436 · Cited by 38
Mechanisms of epigenetic deregulation in lymphoid neoplasms
Jiang, Y., Hatzi, K., & Shaknovich, R. (2013) · Blood · doi:10.1182/blood-2012-12-451799 · Cited by 39
Molecular Pathways: Epigenetic Modulation of Wnt–Glycogen Synthase Kinase-3 Signaling to Target Human Cancer Stem Cells
Benoit, Y. D., Guezguez, B., Boyd, A. L., & Bhatia, M. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2491 · Cited by 40
Targeting Enhancer of Zeste Homolog 2 for the Treatment of Hematological Malignancies and Solid Tumors: Candidate Structure–Activity Relationships Insights and Evolution Prospects
Xia, J., Li, J., Tian, L., Ren, X., Liu, C., & Liang, C. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00047 · Cited by 38
Prostate cancer epigenetics and its clinical implications
Yegnasubramanian, S. (2016) · Asian Journal of Andrology · doi:10.4103/1008-682x.179859 · Cited by 38
Targeting Enhancer of Zeste Homolog 2 as a promising strategy for cancer treatment
Marchesi, I., & Bagella, L. (2016) · World Journal of Clinical Oncology · doi:10.5306/wjco.v7.i2.135 · Cited by 38
Arginine Methyltransferase 1 in the Nucleus Accumbens Regulates Behavioral Effects of Cocaine
Li, Y., Zhu, R., Wang, W., Fu, D., Hou, J., Ji, S., Chen, B., Hu, Z., Shao, X., Yu, X.-R., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0246-15.2015 · Cited by 37
EZH2 knockdown suppresses the growth and invasion of human inflammatory breast cancer cells
Mu, Z., Li, H., Fernandez, S. V., Alpaugh, K. R., Zhang, R., & Cristofanilli, M. (2013) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-32-70 · Cited by 38
miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells
Zhang, W., Lin, J., Wang, P., & Sun, J. H. (2016) · Journal of drug targeting · doi:10.1080/1061186x.2016.1207647 · Cited by 37
Therapeutic Targeting of Epithelial Plasticity Programs: Focus on the Epithelial-Mesenchymal Transition
Malek, R. A., Wang, H., Taparra, K., & Tran, P. T. (2017) · Cells Tissues Organs · doi:10.1159/000447238 · Cited by 40
Histone methyl transferases: A class of epigenetic opportunities to counter uncontrolled cell proliferation
Singh, P. K. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.01.069 · Cited by 38
The Synergistic Anti-Tumor Activity of EZH2 Inhibitor SHR2554 and HDAC Inhibitor Chidamide through ORC1 Reduction of DNA Replication Process in Diffuse Large B Cell Lymphoma
Wang, X., Wang, D., Ding, N., Mi, L., Yu, H., Wu, M., Feng, F., Hu, L., Zhang, Y., Zhong, C., et al. (2021) · Cancers · doi:10.3390/cancers13174249 · Cited by 36
EZH2: An Accomplice of Gastric Cancer
Yu, W., Liu, N., Song, X., Chen, L., Wang, M., Xiao, G., Li, T., Wang, Z., & Zhang, Y. (2023) · Cancers · doi:10.3390/cancers15020425 · Cited by 37
Role of histone methylation in skin cancers: Histone methylation–modifying enzymes as a new class of targets for skin cancer treatment
Sutopo, N. C., Kim, J. H., & Cho, J. Y. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188865 · Cited by 38
Design, Synthesis, and Biological Activity of Substrate Competitive SMYD2 Inhibitors
Cowen, S. D., Russell, D. J., Dakin, L. A., Chen, H., Larsen, N., Godin, R. E., Throner, S. R., Zheng, X., Molina, A., Wu, J., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01303 · Cited by 36
EZH1/2 as targets for cancer therapy
An, R., Li, Y., Lin, Y.-L., Xu, F., Li, M., & Liu, Z. (2022) · Cancer Gene Therapy · doi:10.1038/s41417-022-00555-1 · Cited by 36
Reaction Coupling between Wild-Type and Disease-Associated Mutant EZH2
Swalm, B. M., Knutson, S. K., Warholic, N. M., Jin, L., Kuntz, K. W., Keilhack, H., Smith, J. J., Pollock, R. M., Moyer, M. P., Scott, M. P., et al. (2014) · ACS Chemical Biology · doi:10.1021/cb500548b · Cited by 35
Self-citation
EZH2: The roles in targeted therapy and mechanisms of resistance in breast cancer
Chen, Y., Zhu, H., Luo, Y., Tong, S., & Liu, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116624 · Cited by 36
Chromatin-regulating proteins as targets for cancer therapy
Oike, T., Ogiwara, H., Amornwichet, N., Nakano, T., & Kohno, T. (2014) · Journal of Radiation Research · doi:10.1093/jrr/rrt227 · Cited by 37
Functional roles of enhancer of zeste homolog 2 in gliomas
Yin, Y., Qiu, S., & Peng, Y. (2015) · Gene · doi:10.1016/j.gene.2015.09.080 · Cited by 35
Enhancer of zeste homologue 2 plays an important role in neuroblastoma cell survival independent of its histone methyltransferase activity
Bate-Eya, L. T., Gierman, H. J., Ebus, M. E., Köster, J., Caron, H. N., Versteeg, R., Dolman, M. E. M., & Molenaar, J. J. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2016.12.019 · Cited by 35
Hsp90 inhibition destabilizes Ezh2 protein in alloreactive T cells and reduces graft-versus-host disease in mice
Huang, Q., He, S., Tian, Y., Gu, Y., Chen, P., Li, C., Huang, J., Liu, Y., Yu, H., Jin, M., et al. (2017) · Blood · doi:10.1182/blood-2016-08-735886 · Cited by 35
Development of a high-throughput fluorescence polarization assay for the discovery of EZH2-EED interaction inhibitors
Zhu, M.-R., Du, D., Hu, J., Li, L., Liu, J.-Q., Ding, H., Kong, X., Jiang, H., Chen, K., & Luo, C. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.59 · Cited by 34
Targeting protein methylation: from chemical tools to precision medicines
Dilworth, D., & Baršytė-Lovejoy, D. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03147-9 · Cited by 35
Pharmacological inhibition of noncanonical EED-EZH2 signaling overcomes chemoresistance in prostate cancer
Li, X., Gera, L., Zhang, S., Chen, Y., Lou, L., Wilson, L. M., Xie, Z., Sautto, G. A., Liu, D., Danaher, A., et al. (2021) · Theranostics · doi:10.7150/thno.49235 · Cited by 35
Writing and Rewriting the Epigenetic Code of Cancer Cells: From Engineered Proteins to Small Molecules
Blancafort, P., Jin, J. J., & Frye, S. V. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.080697 · Cited by 34
Elements of the Polycomb Repressor SU(Z)12 Needed for Histone H3-K27 Methylation, the Interface with E(Z), and In Vivo Function
Rai, A. N., Vargas, M. L., Wang, L., Andersen, E., Miller, E., & Simon, J. A. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00307-13 · Cited by 34
Treating lymphoma is now a bit EZ-er
Morin, R. D., Arthur, S. E., & Assouline, S. E. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020002773 · Cited by 34
Fascinating Transformation of SAM-Competitive Protein Methyltransferase Inhibitors from Nucleoside Analogues to Non-Nucleoside Analogues
Talukdar, A., Mukherjee, A., & Bhattacharya, D. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01208 · Cited by 33
EZH2 expression is a prognostic factor in childhood intracranial ependymoma: A Canadian Pediatric Brain Tumor Consortium study
Li, A. M., Dunham, C. P., Tabori, U. Y., Carret, A., McNeely, P. D., Johnston, D. L., Lafay‐Cousin, L., Wilson, B. A., Eisenstat, D. D., Jabado, N., et al. (2015) · Cancer · doi:10.1002/cncr.29198 · Cited by 33
Epigenetic reprogramming in breast cancer: From new targets to new therapies
Katz, T. A., Huang, Y., Davidson, N. E., & Jankowitz, R. C. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.923740 · Cited by 33
Structure–activity relationship studies of SETD8 inhibitors
Ma, A., Yu, W., Xiong, Y., Butler, K. V., Brown, P. J., & Jin, J. J. (2014) · MedChemComm · doi:10.1039/c4md00317a · Cited by 33
Tackling malignant melanoma epigenetically: histone lysine methylation
Orouji, E., & Utikal, J. S. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0583-z · Cited by 33
BET and EZH2 Inhibitors: Novel Approaches for Targeting Cancer
Genta, S., Pirosa, M. C., & Stathis, A. (2019) · Current Oncology Reports · doi:10.1007/s11912-019-0762-x · Cited by 33
Strong expression of EZH2 and accumulation of trimethylated H3K27 in diffuse large B-cell lymphoma independent of cell of origin and EZH2 codon 641 mutation
Zhou, Z. G., Gao, J., Popovic, R., Wolniak, K. L., Parimi, V., Winter, J. N., Licht, J. D., & Chen, Y. (2015) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2015.1006220 · Cited by 33
Roles of enhancer of zeste homolog 2: From skeletal muscle differentiation to rhabdomyosarcoma carcinogenesis
Marchesi, I., Giordano, A., & Bagella, L. (2014) · Cell Cycle · doi:10.4161/cc.27921 · Cited by 33

Authors: Knutson, S. K., Wigle, T. J., Warholic, N. M., Sneeringer, C. J., Allain, C. J., Klaus, C. R., Sacks, J. D., Raimondi, A., Majer, C. R., Song, J., Scott, M. P., Jin, L., Smith, J. J., Olhava, E. J., Chesworth, R., Moyer, M. P., Richon, V. M., Copeland, R. A., Keilhack, H., Pollock, R. M., & Kuntz, K. W.
Affiliations: Epizyme (United States) (US)
Corresponding author: Kuntz, Kevin W
ORCID: Knutson, Sarah K
Wigle, Tim J
Klaus, Christine R
Raimondi, Alejandra
Song, Jeffrey
Jin, Lei
Smith, Jesse J
Copeland, Robert A
Pollock, Roy M
Venue: Nature Chemical Biology
Publisher: Springer Science and Business Media LLC
Published: 2012-09-30
Volume: 8
Issue: 11
Pages: 890-896
ISSN: 1552-4450 (ISSN-L)
1552-4469
DOI: 10.1038/nchembio.1084
OpenAlex: W2017492512
Cited by: 776
References: 46
Citations by year: 2026: 20 · 2025: 29 · 2024: 29 · 2023: 39 · 2022: 38 · 2021: 49 · 2020: 42 · 2019: 44 · 2018: 60 · 2017: 83 · 2016: 78 · 2015: 97 · 2014: 89 · 2013: 69 · 2012: 10
FWCI: 34.74
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Chemical Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: EZH2, H3K27me3, polycomb repressive complex 2, EZH2 inhibitors, non-Hodgkin lymphoma, oncogene addiction, apoptosis, histone methyltransferase inhibitors
MeSH terms: Enhancer of Zeste Homolog 2 Protein, Antineoplastic Agents, Cell Cycle, Dose-Response Relationship, Drug, Enzyme Inhibitors, Histones, Humans, Indazoles, Lymphoma, Lysine, Methylation, Pyridones, Structure-Activity Relationship, Molecular Structure, Cell Death, Point Mutation, Cell Proliferation, Polycomb Repressive Complex 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks