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163. Marholz LJ, Wang W, Zheng Y, Wang X (2016) A fluorescence polarization biophysical assay
for the Naegleria DNA hydroxylase Tet1. ACS Med Chem Lett 7(2):167–171. https://doi.org/
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164. Gross S, Cairns RA, Minden MD et al (2010) Cancer-associated metabolite
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165. Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce
2-hydroxyglutarate. Nature 462:739–744. https://doi.org/10.1038/nature08617
166. Ward PS, Patel J, Wise DR et al (2010) The common feature of leukemia-associated IDH1 and
IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate.
Cancer Cell 17:225–234. https://doi.org/10.1016/j.ccr.2010.01.020
167. Zhao S, Lin Y, Xu W et al (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1
catalytic activity and induce HIF-1α. Science 324:261–265. https://doi.org/10.1126/science.
1170944
168. Opocher G, Schiavi F (2011) Functional consequences of succinate dehydrogenase mutations.
Endocr Pract 17:64–71. https://doi.org/10.4158/EP11070.RA
169. Rose NR, McDonough MA, King ONF et al (2011) Inhibition of 2-oxoglutarate dependent
oxygenases. Chem Soc Rev 40:4364. https://doi.org/10.1039/c0cs00203h
170. Tarhonskaya H, Nowak RP, Johansson C et al (2017) Studies on the interaction of the histone
demethylase KDM5B with tricarboxylic acid cycle intermediates. J Mol Biol 429:2895–2906.
https://doi.org/10.1016/J.JMB.2017.08.007
171. Koivunen P, Hirsilä M, Remes AM et al (2007) Inhibition of hypoxia-inducible factor (HIF)
hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and
stabilization of HIF. J Biol Chem 282:4524–4532. https://doi.org/10.1074/jbc.M610415200
172. Hopkinson RJ, Tumber A, Yapp C et al (2013) 5-carboxy-8-hydroxyquinoline is a broad
spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation. Chem Sci
4:3110. https://doi.org/10.1039/c3sc51122g
286
R. Belle et al.
of 5-hydroxymethylcytosine. Nat Methods 9:75–77. https://doi.org/10.1038/nmeth.1779
154. Wu X, Zhang Y (2017) TET-mediated active DNA demethylation: mechanism, function and
beyond. Nat Rev Genet 18:517–534. https://doi.org/10.1038/nrg.2017.33
155. Shen L, Zhang Y (2012) Enzymatic analysis of tet proteins: key enzymes in the metabolism of
DNA methylation, 1st edn. Elsevier, Amsterdam
156. Liu MY, Denizio JE, Kohli RM (2016) Quantification of oxidized 5-methylcytosine bases and
TET enzyme activity, 1st edn. Elsevier, Amsterdam
157. Song CX, Szulwach KE, Dai Q et al (2013) Genome-wide profiling of 5-formylcytosine
reveals its roles in epigenetic priming. Cell 153:678–691. https://doi.org/10.1016/j.cell.2013.
04.001
158. Nishio K, Belle R, Katoh T et al (2018) Thioether macrocyclic peptides selected against TET1
compact catalytic domain inhibit TET1 catalytic activity. Chembiochem:1–8. https://doi.org/
10.1002/cbic.201800047
159. Xu W, Yang H, Liu Y et al (2011) Oncometabolite 2-hydroxyglutarate is a competitive
inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 19:17–30. https://doi.org/
10.1016/j.ccr.2010.12.014
160. Laukka T, Mariani CJ, Ihantola T et al (2016) Fumarate and succinate regulate expression of
hypoxia-inducible genes via TET enzymes. J Biol Chem 291:4256–4265. https://doi.org/10.
1074/jbc.M115.688762
161. Alves J, Vidugiris G, Goueli SA, Zegzouti H (2018) Bioluminescent high-throughput succinate detection method for monitoring the activity of JMJC histone demethylases and Fe(II)/2oxoglutarate-dependent dioxygenases. SLAS Discov 23:242–254. https://doi.org/10.1177/
2472555217745657
162. Rose NR, Ng SS, Mecinović J et al (2008) Inhibitor scaffolds for 2-oxoglutarate-dependent
histone lysine demethylases. J Med Chem 51:7053–7056. https://doi.org/10.1021/jm800936s
163. Marholz LJ, Wang W, Zheng Y, Wang X (2016) A fluorescence polarization biophysical assay
for the Naegleria DNA hydroxylase Tet1. ACS Med Chem Lett 7(2):167–171. https://doi.org/
10.1021/acsmedchemlett.5b00366
164. Gross S, Cairns RA, Minden MD et al (2010) Cancer-associated metabolite
2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 207:339–344. https://doi.org/10.1084/jem.20092506
165. Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce
2-hydroxyglutarate. Nature 462:739–744. https://doi.org/10.1038/nature08617
166. Ward PS, Patel J, Wise DR et al (2010) The common feature of leukemia-associated IDH1 and
IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate.
Cancer Cell 17:225–234. https://doi.org/10.1016/j.ccr.2010.01.020
167. Zhao S, Lin Y, Xu W et al (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1
catalytic activity and induce HIF-1α. Science 324:261–265. https://doi.org/10.1126/science.
1170944
168. Opocher G, Schiavi F (2011) Functional consequences of succinate dehydrogenase mutations.
Endocr Pract 17:64–71. https://doi.org/10.4158/EP11070.RA
169. Rose NR, McDonough MA, King ONF et al (2011) Inhibition of 2-oxoglutarate dependent
oxygenases. Chem Soc Rev 40:4364. https://doi.org/10.1039/c0cs00203h
170. Tarhonskaya H, Nowak RP, Johansson C et al (2017) Studies on the interaction of the histone
demethylase KDM5B with tricarboxylic acid cycle intermediates. J Mol Biol 429:2895–2906.
https://doi.org/10.1016/J.JMB.2017.08.007
171. Koivunen P, Hirsilä M, Remes AM et al (2007) Inhibition of hypoxia-inducible factor (HIF)
hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and
stabilization of HIF. J Biol Chem 282:4524–4532. https://doi.org/10.1074/jbc.M610415200
172. Hopkinson RJ, Tumber A, Yapp C et al (2013) 5-carboxy-8-hydroxyquinoline is a broad
spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation. Chem Sci
4:3110. https://doi.org/10.1039/c3sc51122g
286
R. Belle et al.