The EED protein–protein interaction inhibitor A-395 inactivates the PRC2 complex
Abstract
Polycomb repressive complex 2 (PRC2) is a regulator of epigenetic states required for development and homeostasis. PRC2 trimethylates histone H3 at lysine 27 (H3K27me3), which leads to gene silencing, and is dysregulated in many cancers. The embryonic ectoderm development (EED) protein is an essential subunit of PRC2 that has both a scaffolding function and an H3K27me3-binding function. Here we report the identification of A-395, a potent antagonist of the H3K27me3 binding functions of EED. Structural studies demonstrate that A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2. Phenotypic effects observed in vitro and in vivo are similar to those of known PRC2 enzymatic inhibitors; however, A-395 retains potent activity against cell lines resistant to the catalytic inhibitors. A-395 represents a first-in-class antagonist of PRC2 protein-protein interactions (PPI) for use as a chemical probe to investigate the roles of EED-containing protein complexes.
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<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
<i>Phaser</i> crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · see citing works
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,671 · see citing works
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262 · see citing works
A gene complex controlling segmentation in Drosophila
Lewis, E. B. (1978) · Nature · doi:10.1038/276565a0 · Cited by 3,813 · see citing works
Krissinel, E., & Henrick, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904026460 · Cited by 3,785 · see citing works
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 · see citing works
The Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347 · see citing works
Niesen, F., Berglund, H., & Vedadi, M. (2007) · Nature Protocols · doi:10.1038/nprot.2007.321 · Cited by 2,420 · see citing works
Self-citationData processing and analysis with the autoPROC toolbox
Vonrhein, C., Flensburg, C., Keller, P., Sharff, A., Smart, O. S., Paciorek, W. A., Womack, T. O., & Bricogne, G. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444911007773 · Cited by 2,084 · see citing works
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations
McCabe, M. T., Ott, H. M., Ganji, G., Korenchuk, S., Thompson, C., Van Aller, G. S., Liu, Y., Graves, A. P., III, A. D. P., Diaz, E., et al. (2012) · Nature · doi:10.1038/nature11606 · Cited by 1,786 · see citing works
Role of histone H2A ubiquitination in Polycomb silencing
Wang, H., Wang, L., Erdjument‐Bromage, H., Vidal, M., Tempst, P., Jones, R. S., & Zhang, Y. (2004) · Nature · doi:10.1038/nature02985 · Cited by 1,770 · see citing works
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 1,670 · see citing works
Self-citationFrequent 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 · see citing works
Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., & Reinberg, D. (2002) · Genes & Development · doi:10.1101/gad.1035902 · Cited by 1,596 · see citing works
Inhibition of PRC2 Activity by a Gain-of-Function H3 Mutation Found in Pediatric Glioblastoma
Lewis, P. W., Müller, M. M., Koletsky, M. S., Cordero, F., Lin, S., Banaszynski, L. A., Garcia, B. A., Muir, T. W., Becher, O. J., & Allis, C. D. (2013) · Science · doi:10.1126/science.1232245 · Cited by 1,345 · see citing works
Epigenetic protein families: a new frontier for drug discovery
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., & Schapira, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3674 · Cited by 1,327 · see citing works
Self-citationMechanisms of Polycomb gene silencing: knowns and unknowns
Simon, J. A., & Kingston, R. E. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2763 · Cited by 1,320 · see citing works
Role of the polycomb protein EED in the propagation of repressive histone marks
Margueron, R., Justin, N., Ohno, K., Sharpe, M. L., Son, J., Drury, W. J., Voigt, P., Martin, S. R., Taylor, W. R., Marco, V. D., et al. (2009) · Nature · doi:10.1038/nature08398 · Cited by 1,203 · see citing works
Shen, X., Liu, Y., Hsu, Y.-J., Fujiwara, Y., Kim, J., Mao, X., Yuan, G.-C., & Orkin, S. H. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.10.016 · Cited by 1,021 · see citing works
Analysis of the coding genome of diffuse large B-cell lymphoma
Pasqualucci, L., Trifonov, V. A., Fabbri, G., Ma, J., Rossi, D., Chiarenza, A., Wells, V. A., Grunn, A., Messina, M., Elliott, O., et al. (2011) · Nature Genetics · doi:10.1038/ng.892 · Cited by 971 · see citing works
The Polycomb-Group GeneEzh2 Is Required for Early Mouse Development
O’Carroll, D., Erhardt, S., Pagani, M., Barton, S. C., Surani, M. A., & Jenuwein, T. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.13.4330-4336.2001 · Cited by 908 · see citing works
High-Density Miniaturized Thermal Shift Assays as a General Strategy for Drug Discovery
Pantoliano, M. W., Petrella, E. C., Kwasnoski, J. D., Lobanov, V. S., Myslik, J. C., Graf, E., Carver, T., Asel, E. D., Springer, B. A., Lane, P. D., et al. (2001) · SLAS DISCOVERY · doi:10.1177/108705710100600609 · Cited by 899 · see citing works
Ezh1 and Ezh2 Maintain Repressive Chromatin through Different Mechanisms
Margueron, R., Li, G., Sarma, K., Blais, A., Zavadil, J., Woodcock, C. L. F., Dynlacht, B. D., & Reinberg, D. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.11.004 · Cited by 889 · see citing works
Transcriptional regulation by Polycomb group proteins
Di Croce, L., & Helin, K. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2669 · Cited by 864 · see citing works
Role of Bmi-1 and Ring1A in H2A Ubiquitylation and Hox Gene Silencing
Cao, R., Tsukada, Y.-I., & Zhang, Y. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.12.002 · Cited by 847 · see citing works
Knutson, S. K., Warholic, N. M., Wigle, T. J., Klaus, C. R., Allain, C. J., Raimondi, A., Scott, M. P., Chesworth, R., Moyer, M. P., Copeland, R. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303800110 · Cited by 794 · see citing works
A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells
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., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1084 · Cited by 776 · see citing works
A model for transmission of the H3K27me3 epigenetic mark
Hansen, K. H., Bracken, A. P., Pasini, D., Dietrich, N., Gehani, S. S., Monrad, A., Rappsilber, J., Lerdrup, M., & Helin, K. (2008) · Nature Cell Biology · doi:10.1038/ncb1787 · Cited by 720 · see citing works
The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression
Chan, K.-M., Fang, D., Gan, H., Hashizume, R., Yu, C., Schroeder, M., Gupta, N., Mueller, S., James, C. D., Jenkins, R., et al. (2013) · Genes & Development · doi:10.1101/gad.217778.113 · Cited by 707 · see citing works
The Polycomb Group Protein Suz12 Is Required for Embryonic Stem Cell Differentiation
Pasini, D., Bracken, A. P., Hansen, J. B., Capillo, M., & Helin, K. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01432-06 · Cited by 696 · see citing works
Sneeringer, C. J., Scott, M. P., Kuntz, K. W., Knutson, S. K., Pollock, R. M., Richon, V. M., & Copeland, R. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012525107 · Cited by 691 · see citing works
Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery
Lo, M.-C., AULABAUGH, A. E., Jin, G., Cowling, R. A., Bard, J., Malamas, M. S., & Ellestad, G. A. (2004) · Analytical Biochemistry · doi:10.1016/j.ab.2004.04.031 · Cited by 688 · see citing works
McCabe, M. T., Graves, A. P., Ganji, G., Diaz, E., Halsey, W. S., Jiang, Y., Smitheman, K. N., Ott, H. M., Pappalardi, M. B., Allen, K. E., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116418109 · Cited by 493 · see citing works
An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1
Konze, K. D., Ma, A., Li, F., Baršytė-Lovejoy, D., Parton, T., MacNevin, C. J., Liu, F., Gao, C., Huang, X., Kuznetsova, E., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb400133j · Cited by 450 · see citing works
Self-citationStructural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2
Justin, N., Zhang, Y., Tarricone, C., Martin, S. R., Chen, S., Underwood, E., Marco, V. D., Haire, L. F., Walker, P. A., Reinberg, D., et al. (2016) · Nature Communications · doi:10.1038/ncomms11316 · Cited by 403 · see citing works
Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2
Jiao, L., & Liu, X. (2015) · Science · doi:10.1126/science.aac4383 · Cited by 402 · see citing works
Levine, S. S., Weiss, A., Erdjument‐Bromage, H., Shao, Z., Tempst, P., & Kingston, R. E. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.17.6070-6078.2002 · Cited by 388 · see citing works
Recognition and Specificity Determinants of the Human Cbx Chromodomains
Kaustov, L., Ouyang, H., Amaya, M. F., Lemak, A. S., Nady, N., Duan, S., Wasney, G. A., Li, Z., Vedadi, M., Schapira, M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.191411 · Cited by 306 · see citing works
Self-citationThe eed mutation disrupts anterior mesoderm production in mice
Faust, C. J., Schumacher, A., Holdener, B. C., & Magnuson, T. (1995) · Development · doi:10.1242/dev.121.2.273 · Cited by 295 · see citing works
Cause and Consequences of Genetic and Epigenetic Alterations in Human Cancer
Sadiković, B., Al-Romaih, K. I., Squire, J. A., & Zieleńska, M. (2008) · Current Genomics · doi:10.2174/138920208785699580 · Cited by 292 · see citing works
A new world of Polycombs: unexpected partnerships and emerging functions
Schwartz, Y. B., & Pirrotta, V. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3603 · Cited by 277 · see citing works
Molecular recognition of histone H3 by the WD40 protein WDR5
Couture, J., Collazo, E., & Trievel, R. C. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1116 · Cited by 256 · see citing works
Xu, C., Bian, C., Yang, W., Galka, M., Ouyang, H., Chen, C., Qiu, W., Liu, H., Jones, A. E., MacKenzie, F., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008937107 · Cited by 221 · see citing works
( R )-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells
Baršytė-Lovejoy, D., Li, F., Oudhoff, M. J., Tatlock, J. H., Dong, A., Zeng, H., Wu, H., Freeman, S. A., Schapira, M., Senisterra, G. A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407358111 · Cited by 187 · see citing works
Self-citationFresquet, V., Rieger, M., Carolis, C., Garcia-Barchino, M. J., & Martinez-Climent, J. A. (2014) · Blood · doi:10.1182/blood-2014-03-560284 · Cited by 187 · see citing works
Brooun, A., Gajiwala, K. S., Deng, Y., Liu, W., Bolaños, B., Bingham, P., He, Y.-A., Diehl, W. C., Grable, N., Kung, P., et al. (2016) · Nature Communications · doi:10.1038/ncomms11384 · Cited by 164 · see citing works
Self-citationGarapaty, S., Nasveschuk, C. G., Gagnon, A., Chan, E. Y., Sandy, P., Busby, J., Balasubramanian, S., Campbell, R., Zhao, F., Bergeron, L., et al. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.09.013 · Cited by 154 · see citing works
Gibaja, V, Shen, F., Harari, J., Korn, J., Ruddy, D., Saenz-Vash, V, Zhai, H., Rejtar, T., Paris, C. G., Yu, Z., et al. (2016) · Oncogene · doi:10.1038/onc.2015.114 · Cited by 149 · see citing works
Thermal Denaturation Assays in Chemical Biology
Senisterra, G. A., Chau, I., & Vedadi, M. (2011) · Assay and Drug Development Technologies · doi:10.1089/adt.2011.0390 · Cited by 148 · see citing works
Self-citationEZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas
Ryan, R. J. H., Nitta, M., Borger, D. R., Zukerberg, L. R., Ferry, J. A., Harris, N. L., Iafrate, A. J., Bernstein, B., Sohani, A. R., & Le, L. P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028585 · Cited by 122 · see citing works
Pappano, W. N., Guo, J. Q., He, Y., Ferguson, D. C., Jagadeeswaran, S., Osterling, D. J., Gao, W., Spence, J. K., Pliushchev, M. A., Sweis, R. F., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131716 · Cited by 100 · see citing works
Self-citationBaker, T. E., Nerle, S., Pritchard, J. R., Zhao, B., Rivera, V. M., Garner, A. P., & Gonzalvez, F. (2015) · Oncotarget · doi:10.18632/oncotarget.5066 · Cited by 78 · see citing works
Hernando, H., Gelato, K. A., Lesche, R., Beckmann, G., Koehr, S., Otto, S., Steigemann, P., & Stresemann, C. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0486 · Cited by 62 · see citing works
EED mutants impair polycomb repressive complex 2 in myelodysplastic syndrome and related neoplasms
Ueda, T., Sanada, M., Matsui, H., Yamasaki, N., Honda, Z.-I., Shih, L.-Y., Mori, H., Inaba, T., Ogawa, S., & Honda, H. (2012) · Leukemia · doi:10.1038/leu.2012.146 · Cited by 54 · see citing works
The structure–activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface
Camerino, M. A., Zhong, N., Dong, A., Dickson, B. M., James, L. I., Baughman, B. M., Norris, J. L., Kireev, D., Janzen, W. P., Arrowsmith, C. H., et al. (2013) · MedChemComm · doi:10.1039/c3md00197k · Cited by 24 · see citing works
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Flagged first, then by citations
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Small molecules in targeted cancer therapy: advances, challenges, and future perspectives
Zhong, L., Li, Y., Xiong, L., Wang, W., Wu, M., Yuan, T., Yang, W. M., Tian, C., Miao, Z., Wang, T., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00572-w · Cited by 1,735 · see citing works
Targeted protein degradation: expanding the toolbox
Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960 · see citing works
Epigenetic tools (The Writers, The Readers and The Erasers) and their implications in cancer therapy
Biswas, S., & Rao, C. M. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.08.021 · Cited by 402 · see citing works
The roles of Polycomb repressive complexes in mammalian development and cancer
Piunti, A., & Shilatifard, A. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00341-1 · Cited by 382 · see citing works
WD40 repeat domain proteins: a novel target class?
Schapira, M., Tyers, M., Torrent, M., & Arrowsmith, C. H. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.179 · Cited by 335 · see citing works
Self-citationInhibitors of Protein Methyltransferases and Demethylases
Kanıskan, H. Ü., Martini, M. L., & Jin, J. J. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00801 · Cited by 320 · see citing works
Chemical and Biochemical Perspectives of Protein Lysine Methylation
Luo, M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00008 · Cited by 288 · see citing works
Xu, R., & Gestwicki, J. E. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.06.004 · Cited by 262 · see citing works
PRC2 is high maintenancePreprint
Yu, J.-R., Lee, C., Oksuz, O., Stafford, J. M., & Reinberg, D. (2019) · Genes & Development · doi:10.1101/gad.325050.119 · Cited by 248 · see citing works
Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease
Bhat, K. P., Kanıskan, H. Ü., Jin, J. J., & Gozani, O. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00108-x · Cited by 243 · see citing works
EED-Targeted PROTACs Degrade EED, EZH2, and SUZ12 in the PRC2 Complex
Hsu, J. H.-R., Rasmusson, T., Robinson, J., Pachl, F., Read, J., Kawatkar, S., O’ Donovan, D. H., Bagal, S., Code, E., Rawlins, P., et al. (2020) · Cell Chemical Biology · doi:10.1016/j.chembiol.2019.11.004 · Cited by 202 · see citing works
Enhancer of zeste homolog 2 (EZH2) inhibitors
Gulati, N., Béguelin, W., & Giulino-Roth, L. G. (2018) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2018.1430795 · Cited by 196 · see citing works
Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancerPreprint
Bracken, A. P., Brien, G. L., & Verrijzer, C. P. (2019) · Genes & Development · doi:10.1101/gad.326066.119 · Cited by 192 · see citing works
Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader
Potjewyd, F., Turner, A. W., Beri, J., Rectenwald, J. M., Norris-Drouin, J. L., Cholensky, S. H., Margolis, D. M., Pearce, K. H., Herring, L. E., & James, L. I. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.11.006 · Cited by 179 · see citing works
RNA-modifying proteins as anticancer drug targets
Boriack‐Sjodin, P. A., Ribich, S. A., & Copeland, R. A. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.71 · Cited by 154 · see citing works
The roles of EZH2 in cancer and its inhibitors
Liu, Y., & Yang, Q. (2023) · Medical Oncology · doi:10.1007/s12032-023-02025-6 · Cited by 147 · see citing works
H3 K27M and EZHIP Impede H3K27-Methylation Spreading by Inhibiting Allosterically Stimulated PRC2
Jain, S. U., Rashoff, A. Q., Krabbenhoft, S. D., Hoelper, D., Do, T. J., Gibson, T. J., Lundgren, S. M., Bondra, E. R., Deshmukh, S., Harutyunyan, A. S., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.09.028 · Cited by 142 · see citing works
Engaging chromatin: PRC2 structure meets function
Chammas, P., Mocavini, I., & Croce, L. D. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0615-2 · Cited by 138 · see citing works
Kung, P., Bingham, P., Brooun, A., Collins, M. R., Deng, Y., Dinh, D. M., Fan, C., Gajiwala, K. S., Grantner, R., Gukasyan, H. J., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01375 · Cited by 138 · see citing works
Self-citationA chemical biology toolbox to study protein methyltransferases and epigenetic signaling
Scheer, S., Ackloo, S. Z., Medina, T. D. S., Schapira, M., Li, F., Ward, J. A., Lewis, A. M., Northrop, J. P., Richardson, P. L., Kanıskan, H. Ü., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07905-4 · Cited by 136 · see citing works
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Lee, C., Yu, J.-R., Kumar, S., Jin, Y., LeRoy, G., Bhanu, N. V., Kaneko, S., Garcia, B. A., Hamilton, A. D., & Reinberg, D. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.020 · Cited by 135 · see citing works
Fioravanti, R., Stazi, G., Zwergel, C., Valente, S., & Mai, A. (2018) · The Chemical Record · doi:10.1002/tcr.201800091 · Cited by 119 · see citing works
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Jones, B. A., Varambally, S., & Arend, R. C. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0437 · Cited by 115 · see citing works
Rugo, H. S., Jacobs, I. A., Sharma, S., Scappaticci, F. A., Paul, T. A., Jensen-Pergakes, K., & Malouf, G. G. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01379-x · Cited by 108 · see citing works
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Zhang, Q., Mckenzie, N., Warneford-Thomson, R., Gail, E. H., Flanigan, S. F., Owen, B. M., Lauman, R., Levina, V., Garcia, B. A., Schittenhelm, R. B., et al. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0197-y · Cited by 104 · see citing works
Building C(sp3)-rich complexity by combining cycloaddition and C–C cross-coupling reactions
Chen, T., Barton, L. M., Lin, Y., Tsien, J., Kossler, D., Bastida, I., Asai, S., Bi, C., Chen, J. S., Shan, M., et al. (2018) · Nature · doi:10.1038/s41586-018-0391-9 · Cited by 88 · see citing works
A cis-acting mechanism mediates transcriptional memory at Polycomb target genes in mammals
Holoch, D., Wassef, M. A., Lövkvist, C., Zielinski, D., Aflaki, S., Lombard, B., Héry, T., Loew, D., Howard, M., & Margueron, R. (2021) · Nature Genetics · doi:10.1038/s41588-021-00964-2 · Cited by 79 · see citing works
Integrated Platform for Expedited Synthesis–Purification–Testing of Small Molecule Libraries
Baranczak, A., Tu, N. P., Marjanovic, J., Searle, P. A., Vasudevan, A., & Djurić, S. W. (2017) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.7b00054 · Cited by 83 · see citing works
Youmans, D. T., Schmidt, J. C., & Cech, T. R. (2018) · Genes & Development · doi:10.1101/gad.311936.118 · Cited by 81 · see citing works
EZH2 Inhibition: A Promising Strategy to Prevent Cancer Immune Editing
Kang, N., Eccleston, M., Clermont, P., Latarani, M., Male, D. K., Wang, Y. Z., & Crea, F. (2020) · Epigenomics · doi:10.2217/epi-2020-0186 · Cited by 76 · see citing works
Targeting Histone Methylation in Cancer
McCabe, M. T., Mohammad, H. P., Barbash, O., & Kruger, R. G. (2017) · The Cancer Journal · doi:10.1097/ppo.0000000000000283 · Cited by 73 · see citing works
Wassef, M. A., Luscan, A., Aflaki, S., Zielinski, D., Jansen, P. W. T. C., Baymaz, H. I., Battistella, A., Kersouani, C., Servant, N., Wallace, M. R., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814634116 · Cited by 63 · see citing works
Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF
Radko-Juettner, S., Yue, H., Myers, J., Carter, R. D., Robertson, A. N., Mittal, P., Zhu, Z., Hansen, B. S., Donovan, K. A., Hunkeler, M., et al. (2024) · Nature · doi:10.1038/s41586-024-07250-1 · Cited by 65 · see citing works
Polycomb complexes in normal and malignant hematopoiesis
Carlo, V. D., Mocavini, I., & Croce, L. D. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201808028 · Cited by 61 · see citing works
Huang, Y. R., Sendzik, M., Zhang, J., Gao, Z., Sun, Y., Wang, L., Gu, J., Zhao, K., Yu, Z., Zhang, L., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c02148 · Cited by 62 · see citing works
Small Molecule Approaches for Targeting the Polycomb Repressive Complex 2 (PRC2) in Cancer
Martin, M. C., Zeng, G., Yu, J., & Schiltz, G. E. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01344 · Cited by 62 · see citing works
Lamb, K. N., Bsteh, D., Dishman, S. N., Moussa, H. F., Fan, H., Stuckey, J. I., Norris, J. L., Cholensky, S. H., Li, D., Wang, J., et al. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.07.013 · Cited by 60 · see citing works
Targeting epigenetic modulators using PROTAC degraders: Current status and future perspective
Webb, T., Craigon, C., & Ciulli, A. (2022) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2022.128653 · Cited by 59 · see citing works
Vleet, T. R. V., Liguori, M. J., Lynch, J. J., Rao, M. S., & Warder, S. E. (2018) · SLAS DISCOVERY · doi:10.1177/2472555218799713 · Cited by 60 · see citing works
Targeting non-bromodomain chromatin readers
Arrowsmith, C. H., & Schapira, M. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0290-2 · Cited by 58 · see citing works
Self-citationOvercoming Clinical Resistance to EZH2 Inhibition Using Rational Epigenetic Combination Therapy
Kazansky, Y., Cameron, D., Mueller, H. S., Demarest, P., Zaffaroni, N., Arrighetti, N., Zuco, V., Kuwahara, Y., Somwar, R., Ladanyi, M., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0110 · Cited by 59 · see citing works
Bashore, F. M., Foley, C. A., Ong, H. W., Rectenwald, J. M., Hanley, R. P., Norris-Drouin, J. L., Cholensky, S. H., Mills, C. A., Pearce, K. H., Herring, L. E., et al. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.2c00804 · Cited by 56 · see citing works
Methyltransferase Inhibitors: Competing with, or Exploiting the Bound Cofactor
de Freitas, R. F., Ivanochko, D., & Schapira, M. (2019) · Molecules · doi:10.3390/molecules24244492 · Cited by 54 · see citing works
Dong, H., Liu, S., Zhang, X., Chen, S., Kang, L., Chen, Y., Ma, S., Fu, X., Liu, Y., Zhang, H., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0428 · Cited by 54 · see citing works
Tomassi, S., Romanelli, A., Zwergel, C., Valente, S., & Mai, A. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00226 · Cited by 56 · see citing works
Di, Y., Jing, X., Hu, K., Wen, X., Ye, L., Zhang, X., Qin, J., Ye, J., Lin, R., Wang, Z., et al. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100909 · Cited by 53 · see citing works
Zenk, F. L., Fleck, J. S., Jansen, S. M. J., Kashanian, B., Eisinger, B., Santel, M., Dupré, J.-S., Camp, J. G., & Treutlein, B. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01652-0 · Cited by 53 · see citing works
Houliston, R. S., Lemak, A. S., Iqbal, A., Ivanochko, D., Duan, S., Kaustov, L., Ong, M. S., Fan, L., Senisterra, G. A., Brown, P. J., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.799700 · Cited by 51 · see citing works
Self-citationDiscovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain
Senisterra, G. A., Zhu, H. Y. H., Luo, X., Zhang, H., Xun, G., Lu, C., Xiao, W., Hajian, T., Loppnau, P., Chau, I., et al. (2018) · SLAS DISCOVERY · doi:10.1177/2472555218766278 · Cited by 51 · see citing works
Self-citationProtein methyltransferase inhibitors as precision cancer therapeutics: a decade of discovery
Copeland, R. A. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2017.0080 · Cited by 51 · see citing works
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 · see citing works
Drugging histone methyltransferases in cancer
Richart, L., & Margueron, R. (2020) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.11.009 · Cited by 49 · see citing works
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 · see citing works
Drug Discovery and Chemical Biology of Cancer Epigenetics
Ribich, S. A., Harvey, D. M., & Copeland, R. A. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.08.020 · Cited by 49 · see citing works
Čermáková, K., & Hodges, H. C. (2018) · Molecules · doi:10.3390/molecules23081958 · Cited by 49 · see citing works
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 48 · see citing works
Zaware, N., & Zhou, M. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.06.012 · Cited by 47 · see citing works
Targeting epigenetic machinery: Emerging novel allosteric inhibitors
Ye, F., Huang, J. L., Wang, H., Luo, C., & Zhao, K. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107406 · Cited by 45 · see citing works
Targeting PRC2 for the treatment of cancer: an updated patent review (2016 - 2020)
Dockerill, M., Gregson, C. L., & O’Donovan, D. H. (2020) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1841167 · Cited by 46 · see citing works
Disease Association and Druggability of WD40 Repeat Proteins
Song, R., Wang, Z.-D., & Schapira, M. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00451 · Cited by 45 · see citing works
Pei, H., Guo, W., Peng, Y., Xiong, H., & Chen, Y. (2022) · Medicinal Research Reviews · doi:10.1002/med.21886 · Cited by 45 · see citing works
Recent progress in developing selective inhibitors of protein methyltransferases
Kanıskan, H. Ü., & Jin, J. J. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.06.013 · Cited by 44 · see citing works
Class I histone deacetylases (HDAC) critically contribute to Ewing sarcoma pathogenesis
Schmidt, O., Nehls, N., Prexler, C., von Heyking, K., Groll, T., Pardon, K., García, H. D., Hensel, T., Gürgen, D., Henssen, A. G., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02125-z · Cited by 44 · see citing works
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 44 · see citing works
Towards a druggable epitranscriptome: Compounds that target RNA modifications in cancer
Berdasco, M., & Esteller, M. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15604 · Cited by 43 · see citing works
PRC2, Chromatin Regulation, and Human Disease: Insights From Molecular Structure and Function
Liu, X., & Liu, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.894585 · Cited by 44 · see citing works
Zhang, Q., Agius, S. C., Flanigan, S. F., Uckelmann, M., Levina, V., Owen, B. M., & Davidovich, C. (2021) · Nature Communications · doi:10.1038/s41467-021-24866-3 · Cited by 42 · see citing works
Exploiting Epigenetic Alterations in Prostate Cancer
Baumgart, S. J., & Haendler, B. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18051017 · Cited by 41 · see citing works
A drug repurposing screening reveals a novel epigenetic activity of hydroxychloroquine
Catalano, R., Rocca, R., Juli, G., Costa, G., Maruca, A., Artese, A., Caracciolo, D., Tagliaferri, P., Alcaro, S., Tassone, P., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.111715 · Cited by 38 · see citing works
The control of polycomb repressive complexes by long noncoding RNAs
Trotman, J. B., Braceros, K. C. A., Cherney, R. E., Murvin, M. M., & Calabrese, J. M. (2021) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1657 · Cited by 37 · see citing works
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 35 · see citing works
Self-citationTargeting 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 · see citing works
Rej, R. K., Wang, C., Lü, J., Wang, M., Petrunak, E. M., Zawacki, K. P., McEachern, D., Fernández‐Salas, E., Yang, C., Wang, L., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00479 · Cited by 35 · see citing works
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 · see citing works
Structure-based view of the druggable genome
Wang, J., Yazdani, S., Han, A., & Schapira, M. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.02.006 · Cited by 34 · see citing works
Rej, R. K., Wang, C., Lü, J., Wang, M., Petrunak, E. M., Zawacki, K. P., McEachern, D., Yang, C., Wang, L., Li, R., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01059 · Cited by 34 · see citing works
Wang, M. Y., Liow, P., Guzman, M. I. T., & Qi, J. (2022) · ACS Chemical Biology · doi:10.1021/acschembio.2c00062 · Cited by 34 · see citing works
Methyllysine binding domains: Structural insight and small molecule probe development
Teske, K. A., & Hadden, M. K. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.04.047 · Cited by 32 · see citing works
Bagal, S. K., Gregson, C. L., O’Donovan, D. H., Pike, K. G., Bloecher, A., Barton, P., Borodovsky, A., Code, E. L., Fillery, S. M., Hsu, J. H.-R., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01161 · Cited by 32 · see citing works
Fragment-Based Discovery of an Apolipoprotein E4 (apoE4) Stabilizer
Petros, A. M., Korepanova, A., Jakob, C. G., Qiu, W., Panchal, S. C., Wang, J., Dietrich, J. D., Brewer, J. T., Pohlki, F., Kling, A., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00178 · Cited by 32 · see citing works
Self-citationPolycomb-group proteins in the initiation and progression of cancer
Zhao, X., & Wu, X. (2021) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2021.03.013 · Cited by 31 · see citing works
Expanding the ligand spaces for E3 ligases for the design of protein degraders
Saleem, R. S. Z., Schwalm, M. P., & Knapp, S. (2024) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2024.117718 · Cited by 29 · see citing works
Curtin, M. L., Pliushchev, M. A., Li, H., Torrent, M., Dietrich, J. D., Jakob, C. G., Zhu, H., Zhao, H., Wang, Y., Ji, Z., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.02.030 · Cited by 30 · see citing works
Self-citationImproved methods for targeting epigenetic reader domains of acetylated and methylated lysine
Engelberg, I. A., Foley, C. A., James, L. I., & Frye, S. V. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2021.03.002 · Cited by 27 · see citing works
Chemical biology and pharmacology of histone lysine methylation inhibitors
Barghout, S. H., Machado, R. A. C., & Baršytė-Lovejoy, D. (2022) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2022.194840 · Cited by 27 · see citing works
Lanzi, C., Arrighetti, N., Pasquali, S., & Cassinelli, G. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115727 · Cited by 27 · see citing works
Möhler, J. S., Schnitzer, T., & Wennemers, H. (2020) · Chemistry - A European Journal · doi:10.1002/chem.202002966 · Cited by 26 · see citing works
Reprogramming CBX8-PRC1 function with a positive allosteric modulator
Suh, J. L., Bsteh, D., Hart, B., Si, Y., Weaver, T., Pribitzer, C., Lau, R., Soni, S., Ogana, H. A. N., Rectenwald, J. M., et al. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.10.003 · Cited by 26 · see citing works
An overview of the development of EED inhibitors to disable the PRC2 function
Liu, K., Zhu, K., & Zhang, H. (2021) · RSC Medicinal Chemistry · doi:10.1039/d1md00274k · Cited by 26 · see citing works
AZD9291 inactivates the PRC2 complex to mediate tumor growth inhibition
Zhang, K., Shen, Q., Fang, Y., Sun, Y.-M., Ding, J., & Chen, Y. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0248-2 · Cited by 25 · see citing works
Targeting Epigenetic protein–protein Interactions With small-molecule Inhibitors
Linhares, B. M., Grembecka, J. E., & Cierpicki, T. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2020-0082 · Cited by 25 · see citing works
Chemical inhibitors targeting histone methylation readers
Huang, X., Chen, Y., Xiao, Q., Shang, X., & Liu, Y. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108614 · Cited by 24 · see citing works
A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins
(2024) · doi:10.1021/acs.jmedchem.4c02010 · Cited by 24 · see citing works
Self-citationDardis, G., Wang, J., Simon, J. M., Wang, G. G., & Baldwin, A. S. (2023) · iScience · doi:10.1016/j.isci.2023.107115 · Cited by 24 · see citing works
ALARM NMR for HTS Triage and Chemical Probe Validation
Dahlin, J. L., Cuellar, M. E., Singh, G., Nelson, K. M., Strasser, J. M., Rappe, T. M., Xia, Y., Veglia, G., & Walters, M. A. (2018) · Current Protocols in Chemical Biology · doi:10.1002/cpch.35 · Cited by 24 · see citing works
Evaluation of EED Inhibitors as a Class of PRC2-Targeted Small Molecules for HIV Latency Reversal
Turner, A. W., Dronamraju, R., Potjewyd, F., James, K. S., Winecoff, D., Kirchherr, J., Archin, N. M., Browne, E. P., Strahl, B. D., Margolis, D. M., et al. (2020) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.9b00514 · Cited by 24 · see citing works
Dunn-Davies, H., Dudnakova, T., Nogara, A. M., Rodor, J., Thomas, A. C., Parish, E., Gautier, P. E., Meynert, A. M., Ulitsky, I., Madeddu, P. R., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102173 · Cited by 23 · see citing works
Yuan, Y., Qi, G., Shen, H., Guo, A., Cao, F., Zhu, Y., Xiao, C., Chang, W., & Zheng, S. (2018) · International Journal of Cancer · doi:10.1002/ijc.31736 · Cited by 23 · see citing works
Polycomb group proteins in cancer: multifaceted functions and strategies for modulation
Wang, S. P., Ordonez‐Rubiano, S. C., Dhiman, A., Jiao, G., Strohmier, B. P., Krusemark, C. J., & Dykhuizen, E. C. (2021) · NAR Cancer · doi:10.1093/narcan/zcab039 · Cited by 23 · see citing works
Targeting EED as a key PRC2 complex mediator toward novel epigenetic therapeutics
Bao, Q., Kumar, A., V, Wu, D., & Zhou, J. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.103986 · Cited by 22 · see citing works
- Authors
- He, Y., Selvaraju, S., Curtin, M. L., Jakob, C. G., Zhu, H., Comess, K. M., Shaw, B., The, J., Lima-Fernandes, E., Szewczyk, M. M., Cheng, D., Klinge, K. L., Li, H.-Q., Pliushchev, M., Algire, M. A., Maag, D., Guo, J., Dietrich, J., Panchal, S. C., Petros, A. M., Sweis, R. F., Torrent, M., Bigelow, L. J., Senisterra, G., Li, F., Kennedy, S., Wu, Q., Osterling, D. J., Lindley, D. J., Gao, W., Galasinski, S., Barsyte-Lovejoy, D., Vedadi, M., Buchanan, F. G., Arrowsmith, C. H., Chiang, G. G., Sun, C., & Pappano, W. N.
- Affiliations
- AbbVie (United States) (US)
- University of Toronto (CA)
- Corresponding author
- Sun, Chaohong
- Pappano, William N
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2017-01-30
- Volume
- 13
- Issue
- 4
- Pages
- 389-395
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2581052617
- Cited by
- 224
- References
- 57
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 23 · 2023: 19 · 2022: 27 · 2021: 31 · 2020: 23 · 2019: 30 · 2018: 28 · 2017: 23 · 2016: 1
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-08-01)
- Open access
- closed
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Canadian Institutes of Health Research
- 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 › Genomics and Chromatin Dynamics
- Keywords
- polycomb repressive complex 2, H3K27me3, protein-protein interaction inhibitors, allosteric inhibition, histone methyltransferase, chemical probes, gene silencing, epigenetic regulation, drug resistance
- MeSH terms
- Antineoplastic Agents, Cell Survival, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Indans, Models, Molecular, Protein Binding, Structure-Activity Relationship, Sulfonamides, Tumor Cells, Cultured, Molecular Structure, Cell Line, Tumor, Cell Proliferation, Polycomb Repressive Complex 2
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