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Takizawa T, Yasumatsu I, Horiuchi T, Nakao A, Suzuki K, Yamasaki T, Nakajima K,
Hayakawa M, Yamazaki T, Yadav AS, Adachi N (2017) Novel orally bioavailable EZH1/2
dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor. Cancer Sci
108(10):2069–2078. https://doi.org/10.1111/cas.13326
59. McCabe MT, Mohammad HP, Barbash O, Kruger RG (2017) Targeting histone methylation in
cancer. Cancer J 23(5):292–301. https://doi.org/10.1097/PPO.0000000000000283
60. Kim W, Bird GH, Neff T, Guo G, Kerenyi MA, Walensky LD, Orkin SH (2013) Targeted
disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. Nat Chem Biol 9
(10):643–650. https://doi.org/10.1038/nchembio.1331
61. Kong X, Chen L, Jiao L, Jiang X, Lian F, Lu J, Zhu K, Du D, Liu J, Ding H, Zhang N, Shen J,
Zheng M, Chen K, Liu X, Jiang H, Luo C (2014) Astemizole arrests the proliferation of cancer
cells by disrupting the EZH2-EED interaction of polycomb repressive complex 2. J Med Chem
57(22):9512–9521. https://doi.org/10.1021/jm501230c
62. Chen H, Gao S, Li J, Liu D, Sheng C, Yao C, Jiang W, Wu J, Chen S, Huang W (2015)
Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent
cancer. Oncotarget 6(15):13049–13059. https://doi.org/10.18632/oncotarget.3790
63. Li L, Zhang H, Zhang M, Zhao M, Feng L, Luo X, Gao Z, Huang Y, Ardayfio O, Zhang JH,
Lin Y, Fan H, Mi Y, Li G, Liu L, Feng L, Luo F, Teng L, Qi W, Ottl J, Lingel A, Bussiere DE,
Yu Z, Atadja P, Lu C, Li E, Gu J, Zhao K (2017) Discovery and molecular basis of a diverse
set of polycomb repressive complex 2 inhibitors recognition by EED. PLoS One 12(1):
e0169855. https://doi.org/10.1371/journal.pone.0169855
64. Lingel A, Sendzik M, Huang Y, Shultz MD, Cantwell J, Dillon MP, Fu X, Fuller J, Gabriel T,
Gu J, Jiang X, Li L, Liang F, McKenna M, Qi W, Rao W, Sheng X, Shu W, Sutton J, Taft B,
Wang L, Zeng J, Zhang H, Zhang M, Zhao K, Lindvall M, Bussiere DE (2017) Structureguided design of EED binders allosterically inhibiting the epigenetic polycomb repressive
complex 2 (PRC2) methyltransferase. J Med Chem 60(1):415–427. https://doi.org/10.1021/
acs.jmedchem.6b01473
65. Huang Y, Zhang J, Yu Z, Zhang H, Wang Y, Lingel A, Qi W, Gu XJ, Zhao K, Shultz MD,
Wang L, Fu X, Sun Y, Zhang Q, Jiang X, Zhang JW, Zhang C, Li L, Zeng J, Feng L, Zhang C,
Liu Y, Zhang M, Zhang L, Zhao M, Gao Z, Liu X, Fang D, Guo H, Mi Y, Gabriel T, Dillon
MP, Atadja P, Oyang C (2017) Discovery of first-in-class, potent and orally bioavailable EED
inhibitor with robust anti-cancer efficacy. J Med Chem 60(6):2215–2226. https://doi.org/10.
1021/acs.jmedchem.6b01576
66. He Y, Selvaraju S, Curtin ML, Jakob CG, Zhu H, Comess KM, Shaw B, The J, LimaFernandes E, Szewczyk MM, Cheng D, Klinge KL, Li HQ, Pliushchev M, Algire MA,
Maag D, Guo J, Dietrich J, Panchal SC, Petros AM, Sweis RF, Torrent M, Bigelow LJ,
Senisterra G, Li F, Kennedy S, Wu Q, Osterling DJ, Lindley DJ, Gao W, Galasinski S,
Barsyte-Lovejoy D, Vedadi M, Buchanan FG, Arrowsmith CH, Chiang GG, Sun C, Pappano
WN (2017) The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat Chem Biol 13(4):389–395. https://doi.org/10.1038/nchembio.2306
67. Qi W, Zhao K, Gu J, Huang Y, Wang Y, Zhang H, Zhang M, Zhang J, Yu Z, Li L, Teng L,
Chuai S, Zhang C, Zhao M, Chan H, Chen Z, Fang D, Fei Q, Feng L, Feng L, Gao Y, Ge H,
Ge X, Li G, Lingel A, Lin Y, Liu Y, Luo F, Shi M, Wang L, Wang Z, Yu Y, Zeng J, Zeng C,
Zhang L, Zhang Q, Zhou S, Oyang C, Atadja P, Li E (2017) An allosteric PRC2 inhibitor
targeting the H3K27me3 binding pocket of EED. Nat Chem Biol 13(4):381–388. https://doi.
org/10.1038/nchembio.2304
68. Barnash KD, The J, Norris-Drouin JL, Cholensky SH, Worley BM, Li F, Stuckey JI,
Brown PJ, Vedadi M, Arrowsmith CH, Frye SV, James LI (2017) Discovery of peptidomimetic ligands of EED as allosteric inhibitors of PRC2. ACS Comb Sci 19(3):161–172.
https://doi.org/10.1021/acscombsci.6b00174
152
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