Koenig A, Billadeau DD (2013) Epigenetic regulation of autophagy by the methyltransferase
G9a. Mol Cell Biol 33(20):3983–3993. https://doi.org/10.1128/MCB.00813-13
6. Renneville A, Van Galen P, Canver MC, McConkey M, Krill-Burger JM, Dorfman DM,
Holson EB, Bernstein BE, Orkin SH, Bauer DE, Ebert BL (2015) EHMT1 and EHMT2
inhibition induces fetal hemoglobin expression. Blood 126(16):1930–1939. https://doi.org/10.
1182/blood-2015-06-649087
7. Kubicek S, O’Sullivan RJ, August EM, Hickey ER, Zhang Q, Teodoro ML, Rea S,
Mechtler K, Kowalski JA, Homon CA, Kelly TA, Jenuwein T (2007) Reversal of
H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell
25(3):473–481. https://doi.org/10.1016/j.molcel.2007.01.017
8. Liu F, Chen X, Allali-Hassani A, Quinn AM, Wigle TJ, Wasney GA, Dong A, Senisterra G,
Chau I, Siarheyeva A, Norris JL, Kireev DB, Jadhav A, Herold JM, Janzen WP, Arrowsmith
CH, Frye SV, Brown PJ, Simeonov A, Vedadi M, Jin J (2010) Protein lysine methyltransferase
G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7aminoalkoxy-quinazolines. J Med Chem 53(15):5844–5857. https://doi.org/10.1021/
jm100478y
9. Liu F, Barsyte-Lovejoy D, Allali-Hassani A, He Y, Herold JM, Chen X, Yates CM, Frye SV,
Brown PJ, Huang J, Vedadi M, Arrowsmith CH, Jin J (2011) Optimization of cellular activity
of G9a inhibitors 7-aminoalkoxy-quinazolines. J Med Chem 54(17):6139–6150. https://doi.
org/10.1021/jm200903z
10. Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ,
Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I,
Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A,
Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV,
Arrowsmith CH, Jin J (2011) A chemical probe selectively inhibits G9a and GLP
methyltransferase activity in cells. Nat Chem Biol 7(8):566–574. https://doi.org/10.1038/
nchembio.599
11. Lehnertz B, Pabst C, Su L, Miller M, Liu F, Yi L, Zhang R, Krosl J, Yung E, Kirschner J,
Rosten P, Underhill TM, Jin J, Hebert J, Sauvageau G, Humphries RK, Rossi FM (2014) The
methyltransferase G9a regulates HoxA9-dependent transcription in AML. Genes Dev 28(4):
317–327. https://doi.org/10.1101/gad.236794.113
12. Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh V, Huang XP, Allali-Hassani A, Janzen
WP, Roth BL, Frye SV, Arrowsmith CH, Brown PJ, Vedadi M, Jin J (2013) Discovery of an
in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem
56(21):8931–8942. https://doi.org/10.1021/jm401480r
13. Kim Y, Lee HM, Xiong Y, Sciaky N, Hulbert SW, Cao X, Everitt JI, Jin J, Roth BL, Jiang YH
(2017) Targeting the histone methyltransferase G9a activates imprinted genes and improves
survival of a mouse model of Prader-Willi syndrome. Nat Med 23(2):213–222. https://doi.org/
10.1038/nm.4257
14. Xiong Y, Li F, Babault N, Dong A, Zeng H, Wu H, Chen X, Arrowsmith CH, Brown PJ, Liu J,
Vedadi M, Jin J (2017) Discovery of potent and selective inhibitors for G9a-like protein (GLP)
lysine methyltransferase. J Med Chem 60(5):1876–1891. https://doi.org/10.1021/acs.
jmedchem.6b01645
15. Sweis RF, Pliushchev M, Brown PJ, Guo J, Li F, Maag D, Petros AM, Soni NB, Tse C,
Vedadi M, Michaelides MR, Chiang GG, Pappano WN (2014) Discovery and development of
potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett 5(2):
205–209. https://doi.org/10.1021/ml400496h
16. Pappano WN, Guo J, He Y, Ferguson D, Jagadeeswaran S, Osterling DJ, Gao W, Spence JK,
Pliushchev M, Sweis RF, Buchanan FG, Michaelides MR, Shoemaker AR, Tse C, Chiang GG
(2015) The histone methyltransferase inhibitor A-366 uncovers a role for G9a/GLP in the
epigenetics of leukemia. PLoS One 10(7):e0131716. https://doi.org/10.1371/journal.pone.
0131716
148
G. Stazi et al.
G9a. Mol Cell Biol 33(20):3983–3993. https://doi.org/10.1128/MCB.00813-13
6. Renneville A, Van Galen P, Canver MC, McConkey M, Krill-Burger JM, Dorfman DM,
Holson EB, Bernstein BE, Orkin SH, Bauer DE, Ebert BL (2015) EHMT1 and EHMT2
inhibition induces fetal hemoglobin expression. Blood 126(16):1930–1939. https://doi.org/10.
1182/blood-2015-06-649087
7. Kubicek S, O’Sullivan RJ, August EM, Hickey ER, Zhang Q, Teodoro ML, Rea S,
Mechtler K, Kowalski JA, Homon CA, Kelly TA, Jenuwein T (2007) Reversal of
H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell
25(3):473–481. https://doi.org/10.1016/j.molcel.2007.01.017
8. Liu F, Chen X, Allali-Hassani A, Quinn AM, Wigle TJ, Wasney GA, Dong A, Senisterra G,
Chau I, Siarheyeva A, Norris JL, Kireev DB, Jadhav A, Herold JM, Janzen WP, Arrowsmith
CH, Frye SV, Brown PJ, Simeonov A, Vedadi M, Jin J (2010) Protein lysine methyltransferase
G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7aminoalkoxy-quinazolines. J Med Chem 53(15):5844–5857. https://doi.org/10.1021/
jm100478y
9. Liu F, Barsyte-Lovejoy D, Allali-Hassani A, He Y, Herold JM, Chen X, Yates CM, Frye SV,
Brown PJ, Huang J, Vedadi M, Arrowsmith CH, Jin J (2011) Optimization of cellular activity
of G9a inhibitors 7-aminoalkoxy-quinazolines. J Med Chem 54(17):6139–6150. https://doi.
org/10.1021/jm200903z
10. Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ,
Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I,
Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A,
Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV,
Arrowsmith CH, Jin J (2011) A chemical probe selectively inhibits G9a and GLP
methyltransferase activity in cells. Nat Chem Biol 7(8):566–574. https://doi.org/10.1038/
nchembio.599
11. Lehnertz B, Pabst C, Su L, Miller M, Liu F, Yi L, Zhang R, Krosl J, Yung E, Kirschner J,
Rosten P, Underhill TM, Jin J, Hebert J, Sauvageau G, Humphries RK, Rossi FM (2014) The
methyltransferase G9a regulates HoxA9-dependent transcription in AML. Genes Dev 28(4):
317–327. https://doi.org/10.1101/gad.236794.113
12. Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh V, Huang XP, Allali-Hassani A, Janzen
WP, Roth BL, Frye SV, Arrowsmith CH, Brown PJ, Vedadi M, Jin J (2013) Discovery of an
in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem
56(21):8931–8942. https://doi.org/10.1021/jm401480r
13. Kim Y, Lee HM, Xiong Y, Sciaky N, Hulbert SW, Cao X, Everitt JI, Jin J, Roth BL, Jiang YH
(2017) Targeting the histone methyltransferase G9a activates imprinted genes and improves
survival of a mouse model of Prader-Willi syndrome. Nat Med 23(2):213–222. https://doi.org/
10.1038/nm.4257
14. Xiong Y, Li F, Babault N, Dong A, Zeng H, Wu H, Chen X, Arrowsmith CH, Brown PJ, Liu J,
Vedadi M, Jin J (2017) Discovery of potent and selective inhibitors for G9a-like protein (GLP)
lysine methyltransferase. J Med Chem 60(5):1876–1891. https://doi.org/10.1021/acs.
jmedchem.6b01645
15. Sweis RF, Pliushchev M, Brown PJ, Guo J, Li F, Maag D, Petros AM, Soni NB, Tse C,
Vedadi M, Michaelides MR, Chiang GG, Pappano WN (2014) Discovery and development of
potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett 5(2):
205–209. https://doi.org/10.1021/ml400496h
16. Pappano WN, Guo J, He Y, Ferguson D, Jagadeeswaran S, Osterling DJ, Gao W, Spence JK,
Pliushchev M, Sweis RF, Buchanan FG, Michaelides MR, Shoemaker AR, Tse C, Chiang GG
(2015) The histone methyltransferase inhibitor A-366 uncovers a role for G9a/GLP in the
epigenetics of leukemia. PLoS One 10(7):e0131716. https://doi.org/10.1371/journal.pone.
0131716
148
G. Stazi et al.