The Clinically Used Iron Chelator Deferasirox Is an Inhibitor of Epigenetic JumonjiC Domain-Containing Histone Demethylases
Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are “epigenetic eraser” enzymes involved in the regulation of gene expression and are emerging drug targets in oncology. We screened a set of clinically used iron chelators and report that they po...
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| Published in | ACS chemical biology Vol. 14; no. 8; pp. 1737 - 1750 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
American Chemical Society
16.08.2019
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| Abstract | Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are “epigenetic eraser” enzymes involved in the regulation of gene expression and are emerging drug targets in oncology. We screened a set of clinically used iron chelators and report that they potently inhibit JMJD2A (KDM4A) in vitro. Mode of action investigations revealed that one compound, deferasirox, is a bona fide active site-binding inhibitor as shown by kinetic and spectroscopic studies. Synthesis of derivatives with improved cell permeability resulted in significant upregulation of histone trimethylation and potent cancer cell growth inhibition. Deferasirox was also found to inhibit human 2OG-dependent hypoxia inducible factor prolyl hydroxylase activity. Therapeutic effects of clinically used deferasirox may thus involve transcriptional regulation through 2OG oxygenase inhibition. Deferasirox might provide a useful starting point for the development of novel anticancer drugs targeting 2OG oxygenases and a valuable tool compound for investigations of KDM function. |
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| AbstractList | Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are “epigenetic eraser” enzymes involved in the regulation of gene expression and are emerging drug targets in oncology. We screened a set of clinically used iron chelators and report that they potently inhibit JMJD2A (KDM4A) in vitro. Mode of action investigations revealed that one compound, deferasirox, is a bona fide active site-binding inhibitor as shown by kinetic and spectroscopic studies. Synthesis of derivatives with improved cell permeability resulted in significant upregulation of histone trimethylation and potent cancer cell growth inhibition. Deferasirox was also found to inhibit human 2OG-dependent hypoxia inducible factor prolyl hydroxylase activity. Therapeutic effects of clinically used deferasirox may thus involve transcriptional regulation through 2OG oxygenase inhibition. Deferasirox might provide a useful starting point for the development of novel anticancer drugs targeting 2OG oxygenases and a valuable tool compound for investigations of KDM function. Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are "epigenetic eraser" enzymes involved in the regulation of gene expression and are emerging drug targets in oncology. We screened a set of clinically used iron chelators and report that they potently inhibit JMJD2A (KDM4A) . Mode of action investigations revealed that one compound, deferasirox, is a active site-binding inhibitor as shown by kinetic and spectroscopic studies. Synthesis of derivatives with improved cell permeability resulted in significant upregulation of histone trimethylation and potent cancer cell growth inhibition. Deferasirox was also found to inhibit human 2OG-dependent hypoxia inducible factor prolyl hydroxylase activity. Therapeutic effects of clinically used deferasirox may thus involve transcriptional regulation through 2OG oxygenase inhibition. Deferasirox might provide a useful starting point for the development of novel anticancer drugs targeting 2OG oxygenases and a valuable tool compound for investigations of KDM function. |
| Author | Diederichs, Sven Ahrens, Theresa D Robaa, Dina Jung, Manfred Roatsch, Martin Hancock, Rebecca L Franz, Henriette Schüle, Roland Barthes, Nicolas P. F Sippl, Wolfgang Hsu, Kuo-Feng Schofield, Christopher J Lassmann, Silke Wilkins, Sarah E Lippl, Kerstin Serrer, Kerstin Moneke, Isabelle Yeh, Tzu-Lan Hoffmann, Inga Tarhonskaya, Hanna Wenzler, Sandra Kawamura, Akane Abboud, Martine I Schleicher, Erik |
| AuthorAffiliation | Division of Cancer Research, Department of Thoracic Surgery, Medical Center-University of Freiburg, Faculty of Medicine Central Clinical Research, Medical Center and Faculty of Medicine University of Freiburg Institute of Physical Chemistry Institute for Surgical Pathology, Medical Center and Faculty of Medicine Division of RNA Biology & Cancer Institute of Pharmaceutical Sciences German Cancer Research Center (DKFZ) Chemistry Research Laboratory Institute of Pharmacy |
| AuthorAffiliation_xml | – name: Chemistry Research Laboratory – name: Institute for Surgical Pathology, Medical Center and Faculty of Medicine – name: Central Clinical Research, Medical Center and Faculty of Medicine – name: Institute of Pharmacy – name: Division of RNA Biology & Cancer – name: Division of Cancer Research, Department of Thoracic Surgery, Medical Center-University of Freiburg, Faculty of Medicine – name: University of Freiburg – name: Institute of Pharmaceutical Sciences – name: German Cancer Research Center (DKFZ) – name: Institute of Physical Chemistry |
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| Cites_doi | 10.1002/cmdc.201600218 10.1023/A:1013302231549 10.1021/acs.orglett.6b00277 10.1111/bph.12045 10.1021/acs.jmedchem.5b01758 10.1016/j.blre.2018.03.002 10.1038/s41598-019-39214-1 10.1002/cmdc.201800377 10.1002/jcb.24423 10.1021/ja201597b 10.1074/jbc.M009458200 10.1016/j.cancergen.2014.11.001 10.1038/ncomms3035 10.1111/bjh.14376 10.1002/ejic.200400363 10.1021/jm1003655 10.1016/j.bmcl.2012.07.091 10.1016/j.bmcl.2019.03.028 10.1039/C6CC09882G 10.1371/journal.pone.0015535 10.2217/epi.13.79 10.1039/C8CC00387D 10.1016/j.bbrc.2007.05.179 10.1038/nature11262 10.1016/j.canlet.2013.04.009 10.1021/jm4012802 10.1016/j.exphem.2013.02.004 10.1016/j.pharmthera.2015.01.002 10.1002/mc.20758 10.1002/anie.201612185 10.1016/j.ejphar.2016.04.026 10.1002/cmdc.201500335 10.1002/jcph.113 10.1016/j.bmc.2011.01.046 10.1002/jcb.24009 10.1016/j.ica.2012.06.011 10.3892/ijo.2012.1618 10.1021/jm800936s 10.1039/b916357c 10.4084/mjhid.2018.066 10.1016/j.celrep.2012.09.033 10.4155/fmc.15.188 10.1126/science.aaw1026 10.1098/rstb.2017.0071 10.1021/cr9900275 10.1016/j.cell.2007.02.005 10.1016/j.ejmech.2018.10.040 10.1038/nature04433 10.1080/15592294.2016.1249089 10.1186/s12957-016-0829-1 10.1124/mol.112.081893 10.1002/chem.200304820 10.3892/ijo.2013.1855 10.1016/j.cell.2006.03.028 10.1016/j.molonc.2012.07.004 10.1021/bi4010914 10.1111/bph.12093 10.1002/anie.201810179 10.2217/cer.15.20 10.4161/15592294.2014.983381 10.1016/B978-0-12-801080-8.00018-1 10.1038/nature04853 10.1038/nrd3674 10.1002/cmdc.200900301 10.2217/epi.12.3 10.1101/cshperspect.a026484 10.1021/acs.jcim.8b00539 10.1021/acs.jmedchem.8b01219 |
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| References | ref9/cit9 ref45/cit45 ref3/cit3 ref27/cit27 ref63/cit63 ref56/cit56 ref16/cit16 ref52/cit52 ref23/cit23 ref31/cit31 ref59/cit59 ref2/cit2 ref34/cit34 ref71/cit71 ref37/cit37 ref20/cit20 ref48/cit48 ref60/cit60 ref17/cit17 ref10/cit10 ref35/cit35 ref53/cit53 ref19/cit19 ref21/cit21 Patani N. (ref8/cit8) 2011; 31 ref42/cit42 ref46/cit46 ref49/cit49 ref13/cit13 ref61/cit61 ref67/cit67 ref24/cit24 ref38/cit38 ref50/cit50 ref64/cit64 ref54/cit54 ref6/cit6 ref36/cit36 ref18/cit18 ref65/cit65 ref11/cit11 ref25/cit25 ref29/cit29 Højrup C. (ref40/cit40) 2019 ref32/cit32 ref14/cit14 Hauser A.-T. (ref39/cit39) 2015 ref57/cit57 ref5/cit5 ref51/cit51 ref43/cit43 ref28/cit28 ref68/cit68 ref26/cit26 ref55/cit55 ref69/cit69 ref12/cit12 ref15/cit15 ref62/cit62 ref66/cit66 ref41/cit41 ref58/cit58 ref22/cit22 ref33/cit33 ref4/cit4 ref30/cit30 ref47/cit47 ref1/cit1 ref44/cit44 ref70/cit70 ref7/cit7 |
| References_xml | – ident: ref23/cit23 doi: 10.1002/cmdc.201600218 – ident: ref70/cit70 doi: 10.1023/A:1013302231549 – ident: ref57/cit57 doi: 10.1021/acs.orglett.6b00277 – ident: ref61/cit61 doi: 10.1111/bph.12045 – ident: ref36/cit36 doi: 10.1021/acs.jmedchem.5b01758 – ident: ref66/cit66 doi: 10.1016/j.blre.2018.03.002 – ident: ref47/cit47 doi: 10.1038/s41598-019-39214-1 – ident: ref25/cit25 doi: 10.1002/cmdc.201800377 – ident: ref60/cit60 doi: 10.1002/jcb.24423 – ident: ref30/cit30 doi: 10.1021/ja201597b – ident: ref49/cit49 doi: 10.1074/jbc.M009458200 – ident: ref14/cit14 doi: 10.1016/j.cancergen.2014.11.001 – ident: ref33/cit33 doi: 10.1038/ncomms3035 – ident: ref44/cit44 doi: 10.1111/bjh.14376 – ident: ref53/cit53 doi: 10.1002/ejic.200400363 – ident: ref31/cit31 doi: 10.1021/jm1003655 – volume: 31 start-page: 4115 year: 2011 ident: ref8/cit8 publication-title: Anticancer Res. contributor: fullname: Patani N. – ident: ref29/cit29 doi: 10.1016/j.bmcl.2012.07.091 – ident: ref35/cit35 doi: 10.1016/j.bmcl.2019.03.028 – ident: ref46/cit46 doi: 10.1039/C6CC09882G – ident: ref26/cit26 doi: 10.1371/journal.pone.0015535 – ident: ref20/cit20 doi: 10.2217/epi.13.79 – ident: ref58/cit58 doi: 10.1039/C8CC00387D – ident: ref9/cit9 doi: 10.1016/j.bbrc.2007.05.179 – ident: ref28/cit28 doi: 10.1038/nature11262 – ident: ref10/cit10 doi: 10.1016/j.canlet.2013.04.009 – ident: ref27/cit27 doi: 10.1021/jm4012802 – ident: ref63/cit63 doi: 10.1016/j.exphem.2013.02.004 – ident: ref17/cit17 doi: 10.1016/j.pharmthera.2015.01.002 – ident: ref13/cit13 doi: 10.1002/mc.20758 – ident: ref59/cit59 doi: 10.1002/anie.201612185 – ident: ref56/cit56 doi: 10.1016/j.ejphar.2016.04.026 – ident: ref21/cit21 doi: 10.1002/cmdc.201500335 – ident: ref68/cit68 doi: 10.1002/jcph.113 – ident: ref37/cit37 doi: 10.1016/j.bmc.2011.01.046 – ident: ref11/cit11 doi: 10.1002/jcb.24009 – ident: ref54/cit54 doi: 10.1016/j.ica.2012.06.011 – ident: ref7/cit7 doi: 10.3892/ijo.2012.1618 – ident: ref24/cit24 doi: 10.1021/jm800936s – ident: ref48/cit48 doi: 10.1039/b916357c – ident: ref45/cit45 doi: 10.4084/mjhid.2018.066 – ident: ref12/cit12 doi: 10.1016/j.celrep.2012.09.033 – ident: ref22/cit22 doi: 10.4155/fmc.15.188 – ident: ref15/cit15 doi: 10.1126/science.aaw1026 – ident: ref43/cit43 doi: 10.1098/rstb.2017.0071 – ident: ref50/cit50 doi: 10.1021/cr9900275 – ident: ref2/cit2 doi: 10.1016/j.cell.2007.02.005 – ident: ref6/cit6 doi: 10.1016/j.ejmech.2018.10.040 – start-page: 265 volume-title: Epigenetic Drug Discovery year: 2019 ident: ref40/cit40 contributor: fullname: Højrup C. – ident: ref3/cit3 doi: 10.1038/nature04433 – ident: ref32/cit32 doi: 10.1080/15592294.2016.1249089 – ident: ref64/cit64 doi: 10.1186/s12957-016-0829-1 – ident: ref69/cit69 doi: 10.1124/mol.112.081893 – ident: ref55/cit55 doi: 10.1002/chem.200304820 – ident: ref62/cit62 doi: 10.3892/ijo.2013.1855 – ident: ref4/cit4 doi: 10.1016/j.cell.2006.03.028 – ident: ref19/cit19 doi: 10.1016/j.molonc.2012.07.004 – ident: ref51/cit51 doi: 10.1021/bi4010914 – ident: ref67/cit67 doi: 10.1111/bph.12093 – ident: ref42/cit42 doi: 10.1002/anie.201810179 – ident: ref65/cit65 doi: 10.2217/cer.15.20 – ident: ref5/cit5 doi: 10.4161/15592294.2014.983381 – start-page: 397 volume-title: Epigenetic Technological Applications year: 2015 ident: ref39/cit39 doi: 10.1016/B978-0-12-801080-8.00018-1 contributor: fullname: Hauser A.-T. – ident: ref71/cit71 doi: 10.1038/nature04853 – ident: ref1/cit1 doi: 10.1038/nrd3674 – ident: ref52/cit52 – ident: ref16/cit16 doi: 10.1002/cmdc.200900301 – ident: ref18/cit18 doi: 10.2217/epi.12.3 – ident: ref38/cit38 doi: 10.1101/cshperspect.a026484 – ident: ref34/cit34 doi: 10.1021/acs.jcim.8b00539 – ident: ref41/cit41 doi: 10.1021/acs.jmedchem.8b01219 |
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| Snippet | Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are “epigenetic eraser” enzymes involved in the... Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are "epigenetic eraser" enzymes involved in the... |
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| SubjectTerms | Catalytic Domain - drug effects Cell Line, Tumor Deferasirox - pharmacology Demethylation - drug effects Enzyme Inhibitors - pharmacology Epigenesis, Genetic - drug effects Histones - metabolism Humans Iron Chelating Agents - pharmacology Jumonji Domain-Containing Histone Demethylases - antagonists & inhibitors Jumonji Domain-Containing Histone Demethylases - chemistry |
| Title | The Clinically Used Iron Chelator Deferasirox Is an Inhibitor of Epigenetic JumonjiC Domain-Containing Histone Demethylases |
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