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2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine
methyltransferase G9a. J Med Chem 52(24):7950–7953. https://doi.org/10.1021/jm901543m
113. Zhang J, Yao D, Jiang Y, Huang J, Yang S, Wang J (2017) Synthesis and biological evaluation
of benzimidazole derivatives as the G9a histone methyltransferase inhibitors that induce
autophagy and apoptosis of breast cancer cells. Bioorg Chem 72:168–181. https://doi.org/
10.1016/j.bioorg.2017.04.005
114. Feng T, Wang H, Zhang X, Sun H, You Q (2014) The discovery of novel histone
lysine methyltransferase G9a inhibitors (part 1): molecular design based on a series of
substituted 2,4-diamino-7-aminoalkoxyquinazoline by molecular-docking-guided 3D quantitative structure-activity relationship studies. Med Chem 10(4):426–440
115. Chen WL, Wang ZH, Feng TT, Li DD, Wang CH, Xu XL, Zhang XJ, You QD, Guo XK
(2016) Discovery, design and synthesis of 6H-anthra[1,9-cd]isoxazol-6-one scaffold as G9a
inhibitor through a combination of shape-based virtual screening and structure-based molecular modification. Bioorg Med Chem 24(22):6102–6108. https://doi.org/10.1016/j.bmc.2016.
09.071
116. Cheng D, Yadav N, King RW, Swanson MS, Weinstein EJ, Bedford MT (2004) Small
molecule regulators of protein arginine methyltransferases. J Biol Chem 279
(23):23892–23899. https://doi.org/10.1074/jbc.M401853200
117. Zhang X, Yang Z, Khan SI, Horton JR, Tamaru H, Selker EU, Cheng X (2003) Structural basis
for the product specificity of histone lysine methyltransferases. Mol Cell 12(1):177–185
118. Mason JS, Morize I, Menard PR, Cheney DL, Hulme C, Labaudiniere RF (1999) New 4-point
pharmacophore method for molecular similarity and diversity applications: overview of the
method and applications, including a novel approach to the design of combinatorial libraries
containing privileged substructures. J Med Chem 42(17):3251–3264. https://doi.org/10.1021/
jm9806998
119. Meng F, Cheng S, Ding H, Liu S, Liu Y, Zhu K, Chen S, Lu J, Xie Y, Li L, Liu R, Shi Z,
Zhou Y, Liu YC, Zheng M, Jiang H, Lu W, Liu H, Luo C (2015) Discovery and optimization
of novel, selective histone methyltransferase SET7 inhibitors by pharmacophore- and dockingbased virtual screening. J Med Chem 58(20):8166–8181. https://doi.org/10.1021/acs.
jmedchem.5b01154
120. Shi YJ, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y (2004)
Histone demethylation mediated by the nuclear arnine oxidase homolog LSD1. Cell 119
(7):941–953. https://doi.org/10.1016/j.cell.2004.12.012
121. Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y
(2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439
(7078):811–816. https://doi.org/10.1038/nature04433
122. Wang GG, Allis CD, Chi P (2007) Chromatin remodeling and cancer, part I: covalent histone
modifications. Trends Mol Med 13(9):363–372. https://doi.org/10.1016/j.molmed.2007.07.
003
123. Lynch JT, Harris WJ, Somervaille TC (2012) LSD1 inhibition: a therapeutic strategy in
cancer? Expert Opin Ther Targets 16(12):1239–1249. https://doi.org/10.1517/14728222.
2012.722206
124. Johansson C, Tumber A, Che K, Cain P, Nowak R, Gileadi C, Oppermann U (2014) The roles
of Jumonji-type oxygenases in human disease. Epigenomics 6(1):89–120. https://doi.org/10.
2217/epi.13.79
125. Chen Y, Yang Y, Wang F, Wan K, Yamane K, Zhang Y, Lei M (2006) Crystal structure of
human histone lysine-specific demethylase 1 (LSD1). Proc Natl Acad Sci U S A 103
(38):13956–13961. https://doi.org/10.1073/pnas.0606381103
Structure-Based Design of Epigenetic Inhibitors
483