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113. Sweis RF, Wang Z, Algire M, Arrowsmith CH, Brown PJ, Chiang GG, Guo J, Jakob CG,
Kennedy S, Li F, Maag D, Shaw B, Soni NB, Vedadi M, Pappano WN (2015) Discovery of
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Gheyi T, Li F, Liu S, Martin JR, Mendel D, Olsen JB, Pelletier L, Shatseva T, Wu S, Zhang
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Vedadi M (2015) LLY-507, a cell-active, potent, and selective inhibitor of protein-lysine
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Ter Laak A, Lang T, Fernandez-Montalvan AE, Badock V, Weinmann H, Hartung IV,
Barsyte-Lovejoy D, Szewczyk M, Kennedy S, Li F, Vedadi M, Brown PJ, Santhakumar V,
Arrowsmith CH, Stellfeld T, Stresemann C (2016) Discovery and characterization of a highly
potent and selective aminopyrazoline-based in vivo probe (BAY-598) for the protein lysine
methyltransferase SMYD2. J Med Chem 59(10):4578–4600. https://doi.org/10.1021/acs.
jmedchem.5b01890
116. Huang L, Xu AM (2017) SET and MYND domain containing protein 3 in cancer. Am J Transl
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117. Mitchell LH, Boriack-Sjodin PA, Smith S, Thomenius M, Rioux N, Munchhof M, Mills JE,
Klaus C, Totman J, Riera TV, Raimondi A, Jacques SL, West K, Foley M, Waters NJ, Kuntz
KW, Wigle TJ, Scott MP, Copeland RA, Smith JJ, Chesworth R (2016) Novel oxindole
sulfonamides and sulfamides: EPZ031686, the first orally bioavailable small molecule
SMYD3 inhibitor. ACS Med Chem Lett 7(2):134–138. https://doi.org/10.1021/
acsmedchemlett.5b00272
118. Van Aller GS, Graves AP, Elkins PA, Bonnette WG, McDevitt PJ, Zappacosta F, Annan RS,
Dean TW, Su DS, Carpenter CL, Mohammad HP, Kruger RG (2016) Structure-based design
of a novel SMYD3 inhibitor that bridges the SAM-and MEKK2-binding pockets.
Structure 24(5):774–781. https://doi.org/10.1016/j.str.2016.03.010
119. McDaniel SL, Strahl BD (2017) Shaping the cellular landscape with Set2/SETD2 methylation.
Cell Mol Life Sci 74(18):3317–3334. https://doi.org/10.1007/s00018-017-2517-x
120. Zhu Y, Zhu L, Lu L, Zhang L, Zhang G, Wang Q, Yang P (2014) Role and mechanism of the
alkylglycerone phosphate synthase in suppressing the invasion potential of human glioma and
hepatic carcinoma cells in vitro. Oncol Rep 32(1):431–436. https://doi.org/10.3892/or.2014.
3189
121. Zheng W, Ibanez G, Wu H, Blum G, Zeng H, Dong A, Li F, Hajian T, Allali-Hassani A,
Amaya MF, Siarheyeva A, Yu W, Brown PJ, Schapira M, Vedadi M, Min J, Luo M (2012)
Sinefungin derivatives as inhibitors and structure probes of protein lysine methyltransferase
SETD2. J Am Chem Soc 134(43):18004–18014. https://doi.org/10.1021/ja307060p
122. Beck DB, Oda H, Shen SS, Reinberg D (2012) PR-Set7 and H4K20me1: at the crossroads of
genome integrity, cell cycle, chromosome condensation, and transcription. Genes Dev 26(4):
325–337. https://doi.org/10.1101/gad.177444.111
156
G. Stazi et al.
SET and MYND domain-containing proteins. Int J Mol Sci 16(1):1406–1428. https://doi.org/
10.3390/ijms16011406
111. Reynoird N, Mazur PK, Stellfeld T, Flores NM, Lofgren SM, Carlson SM, Brambilla E,
Hainaut P, Kaznowska EB, Arrowsmith CH, Khatri P, Stresemann C, Gozani O, Sage J (2016)
Coordination of stress signals by the lysine methyltransferase SMYD2 promotes
pancreatic cancer. Genes Dev 30(7):772–785. https://doi.org/10.1101/gad.275529.115
112. Ferguson AD, Larsen NA, Howard T, Pollard H, Green I, Grande C, Cheung T, GarciaArenas R, Cowen S, Wu J, Godin R, Chen H, Keen N (2011) Structural basis of
substrate methylation and inhibition of SMYD2. Structure 19(9):1262–1273. https://doi.org/
10.1016/j.str.2011.06.011
113. Sweis RF, Wang Z, Algire M, Arrowsmith CH, Brown PJ, Chiang GG, Guo J, Jakob CG,
Kennedy S, Li F, Maag D, Shaw B, Soni NB, Vedadi M, Pappano WN (2015) Discovery of
A-893, a new cell-active benzoxazinone inhibitor of lysine methyltransferase SMYD2.
ACS Med Chem Lett 6(6):695–700. https://doi.org/10.1021/acsmedchemlett.5b00124
114. Nguyen H, Allali-Hassani A, Antonysamy S, Chang S, Chen LH, Curtis C, Emtage S, Fan L,
Gheyi T, Li F, Liu S, Martin JR, Mendel D, Olsen JB, Pelletier L, Shatseva T, Wu S, Zhang
FF, Arrowsmith CH, Brown PJ, Campbell RM, Garcia BA, Barsyte-Lovejoy D, Mader M,
Vedadi M (2015) LLY-507, a cell-active, potent, and selective inhibitor of protein-lysine
methyltransferase SMYD2. J Biol Chem 290(22):13641–13653. https://doi.org/10.1074/jbc.
M114.626861
115. Eggert E, Hillig RC, Koehr S, Stockigt D, Weiske J, Barak N, Mowat J, Brumby T, Christ CD,
Ter Laak A, Lang T, Fernandez-Montalvan AE, Badock V, Weinmann H, Hartung IV,
Barsyte-Lovejoy D, Szewczyk M, Kennedy S, Li F, Vedadi M, Brown PJ, Santhakumar V,
Arrowsmith CH, Stellfeld T, Stresemann C (2016) Discovery and characterization of a highly
potent and selective aminopyrazoline-based in vivo probe (BAY-598) for the protein lysine
methyltransferase SMYD2. J Med Chem 59(10):4578–4600. https://doi.org/10.1021/acs.
jmedchem.5b01890
116. Huang L, Xu AM (2017) SET and MYND domain containing protein 3 in cancer. Am J Transl
Res 9(1):1–14
117. Mitchell LH, Boriack-Sjodin PA, Smith S, Thomenius M, Rioux N, Munchhof M, Mills JE,
Klaus C, Totman J, Riera TV, Raimondi A, Jacques SL, West K, Foley M, Waters NJ, Kuntz
KW, Wigle TJ, Scott MP, Copeland RA, Smith JJ, Chesworth R (2016) Novel oxindole
sulfonamides and sulfamides: EPZ031686, the first orally bioavailable small molecule
SMYD3 inhibitor. ACS Med Chem Lett 7(2):134–138. https://doi.org/10.1021/
acsmedchemlett.5b00272
118. Van Aller GS, Graves AP, Elkins PA, Bonnette WG, McDevitt PJ, Zappacosta F, Annan RS,
Dean TW, Su DS, Carpenter CL, Mohammad HP, Kruger RG (2016) Structure-based design
of a novel SMYD3 inhibitor that bridges the SAM-and MEKK2-binding pockets.
Structure 24(5):774–781. https://doi.org/10.1016/j.str.2016.03.010
119. McDaniel SL, Strahl BD (2017) Shaping the cellular landscape with Set2/SETD2 methylation.
Cell Mol Life Sci 74(18):3317–3334. https://doi.org/10.1007/s00018-017-2517-x
120. Zhu Y, Zhu L, Lu L, Zhang L, Zhang G, Wang Q, Yang P (2014) Role and mechanism of the
alkylglycerone phosphate synthase in suppressing the invasion potential of human glioma and
hepatic carcinoma cells in vitro. Oncol Rep 32(1):431–436. https://doi.org/10.3892/or.2014.
3189
121. Zheng W, Ibanez G, Wu H, Blum G, Zeng H, Dong A, Li F, Hajian T, Allali-Hassani A,
Amaya MF, Siarheyeva A, Yu W, Brown PJ, Schapira M, Vedadi M, Min J, Luo M (2012)
Sinefungin derivatives as inhibitors and structure probes of protein lysine methyltransferase
SETD2. J Am Chem Soc 134(43):18004–18014. https://doi.org/10.1021/ja307060p
122. Beck DB, Oda H, Shen SS, Reinberg D (2012) PR-Set7 and H4K20me1: at the crossroads of
genome integrity, cell cycle, chromosome condensation, and transcription. Genes Dev 26(4):
325–337. https://doi.org/10.1101/gad.177444.111
156
G. Stazi et al.