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Ge X, Li G, Lingel A, Lin Y, Liu Y, Luo F, Shi M, Wang L, Wang Z, Yu Y, Zeng J, Zeng C,
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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
247. Sanulli S, Justin N, Teissandier A, Ancelin K, Portoso M, Caron M, Michaud A, Lombard B,
da Rocha ST, Offer J, Loew D, Servant N, Wassef M, Burlina F, Gamblin SJ, Heard E,
Margueron R (2015) Jarid2 methylation via the PRC2 complex regulates H3K27me3
deposition during cell differentiation. Mol Cell 57(5):769–783. https://doi.org/10.1016/j.
molcel.2014.12.020
248. 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
249. Santiago C, Nguyen K, Schapira M (2011) Druggability of methyl-lysine binding sites.
J Comput Aided Mol Des 25(12):1171–1178. https://doi.org/10.1007/s10822-011-9505-2
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399
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)
Structure-guided 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
244. Huang Y, Zhang J, Yu Z, Zhang H, Wang Y, Lingel A, Qi W, Gu J, Zhao K, Shultz MD,
Wang L, Fu X, Sun Y, Zhang Q, Jiang X, Zhang J, 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 embryonic ectoderm development (EED) inhibitor with robust anticancer
efficacy. J Med Chem 60(6):2215–2226. https://doi.org/10.1021/acs.jmedchem.6b01576
245. 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
246. He Y, Selvaraju S, Curtin ML, Jakob CG, Zhu H, Comess KM, Shaw B, The J,
Lima-Fernandes 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
247. Sanulli S, Justin N, Teissandier A, Ancelin K, Portoso M, Caron M, Michaud A, Lombard B,
da Rocha ST, Offer J, Loew D, Servant N, Wassef M, Burlina F, Gamblin SJ, Heard E,
Margueron R (2015) Jarid2 methylation via the PRC2 complex regulates H3K27me3
deposition during cell differentiation. Mol Cell 57(5):769–783. https://doi.org/10.1016/j.
molcel.2014.12.020
248. 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
249. Santiago C, Nguyen K, Schapira M (2011) Druggability of methyl-lysine binding sites.
J Comput Aided Mol Des 25(12):1171–1178. https://doi.org/10.1007/s10822-011-9505-2
Methyl-Readers and Inhibitors
399