{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:52:21Z","timestamp":1792083141054,"version":"4.4.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM007280"],"award-info":[{"award-number":["T32GM007280"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA230854"],"award-info":[{"award-number":["R01CA230854"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA230854"],"award-info":[{"award-number":["R01CA230854"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA218600"],"award-info":[{"award-number":["R01CA218600"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Health & Human Services | National Institutes of Health"},{"name":"U.S. Department of Health & Human Services | National Institutes of Health"},{"name":"U.S. Department of Health & Human Services | National Institutes of Health"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Chem Biol"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1038\/s41589-019-0421-4","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T17:02:28Z","timestamp":1575910948000},"page":"214-222","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":229,"title":["Discovery of a first-in-class EZH2 selective degrader"],"prefix":"10.1038","volume":"16","author":[{"given":"Anqi","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Stratikopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Su","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieli","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiphaine C.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violetta","family":"Leshchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Rialdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-2105","authenticated-orcid":false,"given":"Brandon","family":"Dale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Lagana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Guccione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Parekh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6656-3514","authenticated-orcid":false,"given":"Ramon","family":"Parsons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-3862","authenticated-orcid":false,"given":"Jian","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"421_CR1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1076997","volume":"298","author":"R Cao","year":"2002","unstructured":"Cao, R. et al. Role of histone H3 lysine 27 methylation in polycomb-group silencing. Science 298, 1039\u20131043 (2002).","journal-title":"Science"},{"key":"421_CR2","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1101\/gad.1035902","volume":"16","author":"A Kuzmichev","year":"2002","unstructured":"Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P. & Reinberg, D. Histone methyltransferase activity associated with a human multiprotein complex containing the enhancer of zeste protein. Genes Dev. 16, 2893\u20132905 (2002).","journal-title":"Genes Dev."},{"key":"421_CR3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature09784","volume":"469","author":"R Margueron","year":"2011","unstructured":"Margueron, R. & Reinberg, D. The polycomb complex PRC2 and its mark in life. Nature 469, 343\u2013349 (2011).","journal-title":"Nature"},{"key":"421_CR4","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nm.4036","volume":"22","author":"KH Kim","year":"2016","unstructured":"Kim, K. H. & Roberts, C. W. M. Targeting EZH2 in cancer. Nat. Med. 22, 128\u2013134 (2016).","journal-title":"Nat. Med."},{"key":"421_CR5","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1021\/acs.chemrev.6b00801","volume":"118","author":"H\u00dc Kaniskan","year":"2018","unstructured":"Kaniskan, H. \u00dc., Martini, M. L. & Jin, J. Inhibitors of protein methyltransferases and demethylases. Chem. Rev. 118, 989\u20131068 (2018).","journal-title":"Chem. Rev."},{"key":"421_CR6","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1021\/cb400133j","volume":"8","author":"KD Konze","year":"2013","unstructured":"Konze, K. D. et al. An orally bioavailable chemical probe of the lysine methyltransferases EZH2 and EZH1. ACS Chem. Biol. 8, 1324\u20131334 (2013).","journal-title":"ACS Chem. Biol."},{"key":"421_CR7","doi-asserted-by":"crossref","first-page":"7617","DOI":"10.1021\/acs.jmedchem.6b00855","volume":"59","author":"X Yang","year":"2016","unstructured":"Yang, X. et al. Structure\u2013activity relationship studies for enhancer of zeste homologue 2 (EZH2) and enhancer of zeste homologue 1 (EZH1) inhibitors. J. Med. Chem. 59, 7617\u20137633 (2016).","journal-title":"J. Med. Chem."},{"key":"421_CR8","doi-asserted-by":"crossref","first-page":"7922","DOI":"10.1073\/pnas.1303800110","volume":"110","author":"SK Knutson","year":"2013","unstructured":"Knutson, S. K. et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc. Natl Acad. Sci. USA 110, 7922\u20137927 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"421_CR9","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/nchembio.1084","volume":"8","author":"SK Knutson","year":"2012","unstructured":"Knutson, S. K. et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat. Chem. Biol. 8, 890\u2013896 (2012).","journal-title":"Nat. Chem. Biol."},{"key":"421_CR10","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature11606","volume":"492","author":"MT McCabe","year":"2012","unstructured":"McCabe, M. T. et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 492, 108\u2013112 (2012).","journal-title":"Nature"},{"key":"421_CR11","doi-asserted-by":"crossref","first-page":"9928","DOI":"10.1021\/acs.jmedchem.6b01315","volume":"59","author":"RG Vaswani","year":"2016","unstructured":"Vaswani, R. G. et al. Identification of (R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a potent and selective inhibitor of histone methyltransferase EZH2, suitable for phase I clinical trials for B-cell lymphomas. J. Med. Chem. 59, 9928\u20139941 (2016).","journal-title":"J. Med. Chem."},{"key":"421_CR12","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1021\/acs.jmedchem.7b01375","volume":"61","author":"PP Kung","year":"2018","unstructured":"Kung, P. P. et al. Optimization of orally bioavailable enhancer of zeste homolog 2 (EZH2) inhibitors using ligand and property-based design strategies: identification of development candidate (R)-5,8-dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2- dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497). J. Med. Chem. 61, 650\u2013665 (2018).","journal-title":"J. Med. Chem."},{"key":"421_CR13","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1126\/science.1227604","volume":"338","author":"K Xu","year":"2012","unstructured":"Xu, K. et al. EZH2 oncogenic activity in castration-resistant prostate cancer cells is polycomb-independent. Science 338, 1465\u20131469 (2012).","journal-title":"Science"},{"key":"421_CR14","doi-asserted-by":"crossref","first-page":"e99599","DOI":"10.15252\/embj.201899599","volume":"38","author":"Y Zhao","year":"2019","unstructured":"Zhao, Y. et al. EZH2 cooperates with gain-of-function p53 mutants to promote cancer growth and metastasis. EMBO J. 38, e99599 (2019).","journal-title":"EMBO J."},{"key":"421_CR15","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1016\/j.celrep.2018.11.035","volume":"25","author":"J Kim","year":"2018","unstructured":"Kim, J. et al. Polycomb- and methylation-independent roles of EZH2 as a transcription activator. Cell Rep. 25, 2808\u20132820 (2018).","journal-title":"Cell Rep."},{"key":"421_CR16","doi-asserted-by":"crossref","first-page":"5463","DOI":"10.1002\/cncr.27581","volume":"118","author":"NU Lin","year":"2012","unstructured":"Lin, N. U. et al. Clinicopathologic features, patterns of recurrence and survival among women with triple-negative breast cancer in the national comprehensive cancer network. Cancer 118, 5463\u20135472 (2012).","journal-title":"Cancer"},{"key":"421_CR17","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1002\/cncr.25961","volume":"117","author":"F Lara-Medina","year":"2011","unstructured":"Lara-Medina, F. et al. Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis and association with menopausal status, body mass index and parity. Cancer 117, 3658\u20133669 (2011).","journal-title":"Cancer"},{"key":"421_CR18","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1093\/annonc\/mdp492","volume":"20","author":"O Gluz","year":"2009","unstructured":"Gluz, O. et al. Triple-negative breast cancer\u2014current status and future directions. Ann. Oncol. 20, 1913\u20131927 (2009).","journal-title":"Ann. Oncol."},{"key":"421_CR19","doi-asserted-by":"crossref","first-page":"11606","DOI":"10.1073\/pnas.1933744100","volume":"100","author":"CG Kleer","year":"2003","unstructured":"Kleer, C. G. et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl Acad. Sci. USA 100, 11606\u201311611 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"421_CR20","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/nature01075","volume":"419","author":"S Varambally","year":"2002","unstructured":"Varambally, S. et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419, 624\u2013629 (2002).","journal-title":"Nature"},{"key":"421_CR21","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.molonc.2012.06.002","volume":"6","author":"K Holm","year":"2012","unstructured":"Holm, K. et al. Global H3K27 trimethylation and EZH2 abundance in breast tumor subtypes. Mol. Oncol. 6, 494\u2013506 (2012).","journal-title":"Mol. Oncol."},{"key":"421_CR22","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1093\/emboj\/cdg542","volume":"22","author":"AP Bracken","year":"2003","unstructured":"Bracken, A. P. et al. EZH2 is downstream of the pRB\u2010E2F pathway, essential for proliferation and amplified in cancer. EMBO J. 22, 5323\u20135335 (2003).","journal-title":"EMBO J."},{"key":"421_CR23","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1200\/JCO.2005.01.5180","volume":"24","author":"IM Bachmann","year":"2006","unstructured":"Bachmann, I. M. et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate and breast. J. Clin. Oncol. 24, 268\u2013273 (2006).","journal-title":"J. Clin. Oncol."},{"key":"421_CR24","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1158\/0008-5472.CAN-05-4300","volume":"66","author":"L Ding","year":"2006","unstructured":"Ding, L., Erdmann, C., Chinnaiyan, A. M., Merajver, S. D. & Kleer, C. G. Identification of EZH2 as a molecular marker for a precancerous state in morphologically normal breast tissues. Cancer Res. 66, 4095\u20134099 (2006).","journal-title":"Cancer Res."},{"key":"421_CR25","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/onc.2008.433","volume":"28","author":"ME Gonzalez","year":"2009","unstructured":"Gonzalez, M. E. et al. Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1. Oncogene 28, 843\u2013853 (2009).","journal-title":"Oncogene"},{"key":"421_CR26","doi-asserted-by":"crossref","first-page":"e5011","DOI":"10.1371\/journal.pone.0005011","volume":"4","author":"X Yang","year":"2009","unstructured":"Yang, X. et al. CDKN1C (p57KIP2) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cells. PLoS One 4, e5011 (2009).","journal-title":"PLoS One"},{"key":"421_CR27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ccr.2010.10.035","volume":"19","author":"CJ Chang","year":"2011","unstructured":"Chang, C. J. et al. EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-beta-catenin signaling. Cancer Cell 19, 86\u2013100 (2011).","journal-title":"Cancer Cell"},{"key":"421_CR28","doi-asserted-by":"crossref","DOI":"10.1186\/s13148-015-0118-9","volume":"7","author":"E Curry","year":"2015","unstructured":"Curry, E. et al. Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological efficacy in breast cancer cells. Clin. Epigenetics 7, 84 (2015).","journal-title":"Clin. Epigenetics"},{"key":"421_CR29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrd.2016.211","volume":"16","author":"AC Lai","year":"2017","unstructured":"Lai, A. C. & Crews, C. M. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov. 16, 101\u2013114 (2017).","journal-title":"Nat. Rev. Drug Discov."},{"key":"421_CR30","doi-asserted-by":"crossref","first-page":"11269","DOI":"10.1021\/acs.chemrev.7b00077","volume":"117","author":"GM Burslem","year":"2017","unstructured":"Burslem, G. M. & Crews, C. M. Small-molecule modulation of protein homeostasis. Chem. Rev. 117, 11269\u201311301 (2017).","journal-title":"Chem. Rev."},{"key":"421_CR31","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/487308a","volume":"487","author":"TK Neklesa","year":"2012","unstructured":"Neklesa, T. K. & Crews, C. M. Greasy tags for protein removal. Nature 487, 308\u2013309 (2012).","journal-title":"Nature"},{"key":"421_CR32","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1038\/nchembio.1658","volume":"10","author":"T Xie","year":"2014","unstructured":"Xie, T. et al. Pharmacological targeting of the pseudokinase Her3. Nat. Chem. Biol. 10, 1006\u20131012 (2014).","journal-title":"Nat. Chem. Biol."},{"key":"421_CR33","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11316","volume":"7","author":"N Justin","year":"2016","unstructured":"Justin, N. et al. Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2. Nat. Commun. 7, 11316 (2016).","journal-title":"Nat. Commun."},{"key":"421_CR34","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11384","volume":"7","author":"A Brooun","year":"2016","unstructured":"Brooun, A. et al. Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance. Nat. Commun. 7, 11384 (2016).","journal-title":"Nat. Commun."},{"key":"421_CR35","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ccell.2019.07.003","volume":"36","author":"JY Fong","year":"2019","unstructured":"Fong, J. Y. et al. Therapeutic targeting of RNA splicing catalysis through inhibition of protein arginine methylation. Cancer Cell 36, 194\u2013209 (2019).","journal-title":"Cancer Cell"},{"key":"421_CR36","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1182\/blood-2014-06-581082","volume":"125","author":"B Xu","year":"2015","unstructured":"Xu, B. et al. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood 125, 346\u2013357 (2015).","journal-title":"Blood"},{"key":"421_CR37","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nrd3976","volume":"12","author":"C Hetz","year":"2013","unstructured":"Hetz, C., Chevet, E. & Harding, H. P. Targeting the unfolded protein response in disease. Nat. Rev. Drug Discov. 12, 703 (2013).","journal-title":"Nat. Rev. Drug Discov."},{"key":"421_CR38","doi-asserted-by":"crossref","first-page":"7448","DOI":"10.1128\/MCB.23.21.7448-7459.2003","volume":"23","author":"A-H Lee","year":"2003","unstructured":"Lee, A.-H., Iwakoshi, N. N. & Glimcher, L. H. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol. Cell Biol. 23, 7448\u20137459 (2003).","journal-title":"Mol. Cell Biol."},{"key":"421_CR39","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0092-8674(01)00611-0","volume":"107","author":"H Yoshida","year":"2001","unstructured":"Yoshida, H., Matsui, T., Yamamoto, A., Okada, T. & Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107, 881\u2013891 (2001).","journal-title":"Cell"},{"key":"421_CR40","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41419-017-0164-7","volume":"9","author":"A Cano-Gonz\u00e1lez","year":"2018","unstructured":"Cano-Gonz\u00e1lez, A., Mauro-Lizcano, M., Iglesias-Serret, D., Gil, J. & L\u00f3pez-Rivas, A. Involvement of both caspase-8 and Noxa-activated pathways in endoplasmic reticulum stress-induced apoptosis in triple-negative breast tumor cells. Cell Death Dis. 9, 134 (2018).","journal-title":"Cell Death Dis."},{"key":"421_CR41","volume":"11","author":"S Guo","year":"2016","unstructured":"Guo, S. et al. EZH2 overexpression in different immunophenotypes of breast carcinoma and association with clinicopathologic features. Diagn. Pathol. 11, 41 (2016).","journal-title":"Diagn. Pathol."},{"key":"421_CR42","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s10549-011-1591-2","volume":"132","author":"SH Alford","year":"2012","unstructured":"Alford, S. H., Toy, K., Merajver, S. D. & Kleer, C. G. Increased risk for distant metastasis in patients with familial early-stage breast cancer and high EZH2 expression. Breast Cancer Res. Treat. 132, 429\u2013437 (2012).","journal-title":"Breast Cancer Res. Treat."},{"key":"421_CR43","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/sj.embor.7400779","volume":"7","author":"E Szegezdi","year":"2006","unstructured":"Szegezdi, E., Logue, S. E., Gorman, A. M. & Samali, A. Mediators of endoplasmic reticulum stress\u2010induced apoptosis. EMBO Rep. 7, 880\u2013885 (2006).","journal-title":"EMBO Rep."},{"key":"421_CR44","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/nchembio.1331","volume":"9","author":"W Kim","year":"2013","unstructured":"Kim, W. et al. Targeted disruption of the EZH2\u2013EED complex inhibits EZH2-dependent cancer. Nat. Chem. Biol. 9, 643\u2013650 (2013).","journal-title":"Nat. Chem. Biol."},{"key":"421_CR45","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1101\/gad.1524107","volume":"21","author":"J Tan","year":"2007","unstructured":"Tan, J. et al. Pharmacologic disruption of polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev. 21, 1050\u20131063 (2007).","journal-title":"Genes Dev."},{"key":"421_CR46","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.bbrc.2013.07.128","volume":"438","author":"J-K Lee","year":"2013","unstructured":"Lee, J.-K. & Kim, K.-C. DZNep, inhibitor of S-adenosylhomocysteine hydrolase, down-regulates expression of SETDB1 H3K9me3 HMTase in human lung cancer cells. Biochem. Biophys. Res. Commun. 438, 647\u2013652 (2013).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"421_CR47","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1158\/1535-7163.MCT-09-0013","volume":"8","author":"TB Miranda","year":"2009","unstructured":"Miranda, T. B. et al. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol. Cancer Ther. 8, 1579\u20131588 (2009).","journal-title":"Mol. Cancer Ther."},{"key":"421_CR48","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.15252\/embj.201694058","volume":"36","author":"X Wang","year":"2017","unstructured":"Wang, X. et al. A covalently bound inhibitor triggers EZH2 degradation through ChIP\u2010mediated ubiquitination. EMBO J. 36, 1243\u20131260 (2017).","journal-title":"EMBO J."},{"key":"421_CR49","doi-asserted-by":"crossref","first-page":"12095","DOI":"10.1073\/pnas.0406731102","volume":"102","author":"S Kasibhatla","year":"2005","unstructured":"Kasibhatla, S. et al. A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid. Proc. Natl Acad. Sci. USA 102, 12095\u201312100 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"421_CR50","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1021\/jm901137j","volume":"53","author":"JB Baell","year":"2010","unstructured":"Baell, J. B. & Holloway, G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem. 53, 2719\u20132740 (2010).","journal-title":"J. Med. Chem."},{"key":"421_CR51","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature19112","volume":"537","author":"A Manglik","year":"2016","unstructured":"Manglik, A. et al. Structure-based discovery of opioid analgesics with reduced side effects. Nature 537, 185\u2013190 (2016).","journal-title":"Nature"},{"key":"421_CR52","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","volume":"14","author":"R Patro","year":"2017","unstructured":"Patro, R., Duggal, G., Love, M. I., Irizarry, R. A. & Kingsford, C. Salmon provides fast and bias-aware quantification of transcript expression. Nat. Methods 14, 417\u2013419 (2017).","journal-title":"Nat. Methods"},{"key":"421_CR53","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","volume":"45","author":"JN Weinstein","year":"2013","unstructured":"Weinstein, J. N. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat. Genet. 45, 1113\u20131120 (2013).","journal-title":"Nat. Genet"},{"key":"421_CR54","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.2","volume":"4","author":"C Soneson","year":"2016","unstructured":"Soneson, C., Love, M. & Robinson, M. Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences. F1000Research 4, 1521 (2016).","journal-title":"F1000Research"},{"key":"421_CR55","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/1471-2105-10-161","volume":"10","author":"W Luo","year":"2009","unstructured":"Luo, W., Friedman, M. S., Shedden, K., Hankenson, K. D. & Woolf, P. J. GAGE: generally applicable gene set enrichment for pathway analysis. BMC Bioinformatics 10, 161 (2009).","journal-title":"BMC Bioinformatics"},{"key":"421_CR56","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/bioinformatics\/btt285","volume":"29","author":"W Luo","year":"2013","unstructured":"Luo, W. & Brouwer, C. Pathview: an R\/Bioconductor package for pathway-based data integration and visualization. Bioinformatics 29, 1830\u20131831 (2013).","journal-title":"Bioinformatics"},{"key":"421_CR57","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"421_CR58","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","volume":"34","author":"VK Mootha","year":"2003","unstructured":"Mootha, V. K. et al. PGC-1\u03b1-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267\u2013273 (2003).","journal-title":"Nat. Genet."}],"container-title":["Nature Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41589-019-0421-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41589-019-0421-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41589-019-0421-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T22:28:29Z","timestamp":1684621709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41589-019-0421-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,9]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["421"],"URL":"https:\/\/doi.org\/10.1038\/s41589-019-0421-4","relation":{},"ISSN":["1552-4450","1552-4469"],"issn-type":[{"value":"1552-4450","type":"print"},{"value":"1552-4469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,9]]},"assertion":[{"value":"9 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.J., R.P., A.M., E.S. and X.Y. are inventors for a patent application filed by the Icahn School of Medicine at Mount Sinai. J.J. is an equity shareholder and consultant of Cullgen.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}