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87. Castellano S, Kuck D, Viviano M et al (2011) Synthesis and biochemical evaluation of δ(2)isoxazoline derivatives as DNA methyltransferase 1 inhibitors. J Med Chem 54:7663–7677.
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89. Fagan RL, Cryderman DE, Kopelovich L et al (2013) Laccaic acid A is a direct,
DNA-competitive inhibitor of DNA methyltransferase 1. J Biol Chem 288:23858–23867.
https://doi.org/10.1074/jbc.M113.480517
90. Ceccaldi A, Rajavelu A, Ragozin S et al (2013) Identification of novel inhibitors of DNA
methylation by screening of a chemical library. ACS Chem Biol 8:543–548. https://doi.org/10.
1021/cb300565z
91. Kilgore JA, Du X, Melito L et al (2013) Identification of DNMT1 selective antagonists using a
novel scintillation proximity assay. J Biol Chem 288:19673–19684. https://doi.org/10.1074/
jbc.M112.443895
92. Chen S, Wang Y, Zhou W et al (2014) Identifying novel selective non-nucleoside DNA
methyltransferase 1 inhibitors through docking-based virtual screening. J Med Chem
57:9028–9041. https://doi.org/10.1021/jm501134e
282
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epileptiform activity in vitro and in vivo. PLoS One 8:e76299. https://doi.org/10.1371/journal.
pone.0076299
76. Zhang S, Tang B, Fan C et al (2015) Effect of DNMT inhibitor on bovine parthenogenetic
embryo development. Biochem Biophys Res Commun 466:505–511. https://doi.org/10.1016/
j.bbrc.2015.09.060
77. Meadows JP, Guzman-Karlsson MC, Phillips S et al (2015) DNA methylation regulates
neuronal glutamatergic synaptic scaling. Sci Signal 8:ra61. https://doi.org/10.1126/scisignal.
aab0715
78. Chestnut BA, Chang Q, Price A et al (2011) Epigenetic regulation of motor neuron cell death
through DNA methylation. J Neurosci 31:16619–16636. https://doi.org/10.1523/
JNEUROSCI.1639-11.2011
79. Rondelet G, Fleury L, Faux C et al (2017) Inhibition studies of DNA methyltransferases by
maleimide derivatives of RG108 as non-nucleoside inhibitors. Future Med Chem
9:1465–1481. https://doi.org/10.4155/fmc-2017-0074
80. Datta J, Ghoshal K, Denny WA et al (2009) A new class of quinoline-based DNA
hypomethylating agents reactivates tumor suppressor genes by blocking DNA
methyltransferase 1 activity and inducing its degradation. Cancer Res 69:4277–4285. https://
doi.org/10.1158/0008-5472.CAN-08-3669
81. Gros C, Fleury L, Nahoum V et al (2015) New insights on the mechanism of quinoline-based
DNA methyltransferase inhibitors. J Biol Chem 290:6293–6302. https://doi.org/10.1074/jbc.
M114.594671
82. Valente S, Liu Y, Schnekenburger M et al (2014) Selective non-nucleoside inhibitors of
human DNA methyltransferases active in cancer including in cancer stem cells. J Med
Chem 57:701–713. https://doi.org/10.1021/jm4012627
83. Ceccaldi A, Rajavelu A, Champion C et al (2011) C5-DNA methyltransferase inhibitors: from
screening to effects on zebrafish embryo development. Chembiochem 12:1337–1345. https://
doi.org/10.1002/cbic.201100130
84. Villar-Garea A, Fraga MF, Espada J, Esteller M (2003) Procaine is a DNA-demethylating
agent with growth-inhibitory effects in human cancer cells. Cancer Res 63:4984–4989
85. Lee BH, Yegnasubramanian S, Lin X, Nelson WG (2005) Procainamide is a specific inhibitor
of DNA methyltransferase 1. J Biol Chem 280:40749–40756. https://doi.org/10.1074/jbc.
M505593200
86. Castellano S, Kuck D, Sala M et al (2008) Constrained analogues of procaine as novel small
molecule inhibitors of DNA methyltransferase-1. J Med Chem 51:2321–2325. https://doi.org/
10.1021/jm7015705
87. Castellano S, Kuck D, Viviano M et al (2011) Synthesis and biochemical evaluation of δ(2)isoxazoline derivatives as DNA methyltransferase 1 inhibitors. J Med Chem 54:7663–7677.
https://doi.org/10.1021/jm2010404
88. Halby L, Champion C, Sénamaud-Beaufort C et al (2012) Rapid synthesis of new DNMT
inhibitors derivatives of procainamide. Chembiochem 13:157–165. https://doi.org/10.1002/
cbic.201100522
89. Fagan RL, Cryderman DE, Kopelovich L et al (2013) Laccaic acid A is a direct,
DNA-competitive inhibitor of DNA methyltransferase 1. J Biol Chem 288:23858–23867.
https://doi.org/10.1074/jbc.M113.480517
90. Ceccaldi A, Rajavelu A, Ragozin S et al (2013) Identification of novel inhibitors of DNA
methylation by screening of a chemical library. ACS Chem Biol 8:543–548. https://doi.org/10.
1021/cb300565z
91. Kilgore JA, Du X, Melito L et al (2013) Identification of DNMT1 selective antagonists using a
novel scintillation proximity assay. J Biol Chem 288:19673–19684. https://doi.org/10.1074/
jbc.M112.443895
92. Chen S, Wang Y, Zhou W et al (2014) Identifying novel selective non-nucleoside DNA
methyltransferase 1 inhibitors through docking-based virtual screening. J Med Chem
57:9028–9041. https://doi.org/10.1021/jm501134e
282
R. Belle et al.