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Inhibitors of JmjC-Containing Histone Demethylases

  • Miranda Wright
  • Paul E. Brennan
  • Akane KawamuraEmail author
Chapter
Part of the Topics in Medicinal Chemistry book series

Abstract

Histone demethylases (KDMs) catalyse the removal of N-methyl marks on histones and play important roles in epigenetic regulation. Abnormal histone methylation and dysregulation of KDMs have been linked to multiple diseases, and KDMs are emerging as promising therapeutic targets. This chapter provides an overview of JmjC-domain-containing KDMs (JmjC-KDMs), with a particular focus on recent advances in JmjC-KDM inhibitor development from a structural perspective.

Keywords

2OG oxygenases JmjC histone demethylases KDMs 

Abbreviations

2,4-PDCA

2,4-Pyridine dicarboxylate

2OG

2-Oxoglutarate

8HQ

8-Hydroxyquinoline

Bpy

4′-Carboxy 2,2′-bipyridine

H3

Histone H3

HMT

Histone methyltransferase

JmjC

Jumonji-C

KDM

Lysine demethylase

Kmen

Methylated lysine (n = 1, mono-; n = 2, di-; n = 3, tri-)

NOG

N-oxalylglycine

PHD-finger

Plant homeodomain finger

Notes

Acknowledgement and Funding

MW is supported by the EPSRC Centre for Doctoral Training in Synthesis for Biology and Medicine (EP/L015838/1). AK gratefully acknowledges the Royal Society for the Dorothy Hodgkin Fellowship, the European Research Council Starting Grant (EPITOOLS-679479) and Cancer Research UK Programme Grant (C8717/A18245). The SGC is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, Merck KGaA Darmstadt Germany, MSD, Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, São Paulo Research Foundation-FAPESP, Takeda and Wellcome [106169/ZZ14/Z]. The authors acknowledge the EU COST Action CM1406. We apologise for the incomplete citations and for the research that we were not able to cite due to space constraints.

Compliance and Ethical Standards

Conflict of Interest: The authors declare that they have no conflict of interest.

Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Nature Switzerland AG  2019

Authors and Affiliations

  • Miranda Wright
    • 1
    • 2
  • Paul E. Brennan
    • 1
    • 2
  • Akane Kawamura
    • 3
    • 4
    Email author
  1. 1.Structural Genomics Consortium (SGC)University of OxfordOxfordUK
  2. 2.Nuffield Department of Medicine, Target Discovery InstituteUniversity of OxfordOxfordUK
  3. 3.Chemistry Research Laboratory, Department of ChemistryUniversity of OxfordOxfordUK
  4. 4.Radcliffe Department of Medicine, Wellcome Centre for Human GeneticsUniversity of OxfordOxfordUK

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