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Investigations on small molecule inhibitors targeting the histone H3K4 tri-methyllysine binding PHD-finger of JmjC histone demethylases

Lookup NU author(s): Professor Akane Kawamura



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 The Authors. Plant homeodomain (PHD) containing proteins are important epigenetic regulators and are of interest as potential drug targets. Inspired by the amiodarone derivatives reported to inhibit the PHD finger 3 of KDM5A (KDM5A(PHD3)), a set of compounds were synthesised. Amiodarone and its derivatives were observed to weakly disrupt the interactions of a histone H3K4me3 peptide with KDM5A(PHD3). Selected amiodarone derivatives inhibited catalysis of KDM5A, but in a PHD-finger independent manner. Amiodarone derivatives also bind to H3K4me3-binding PHD-fingers from the KDM7 subfamily. Further work is required to develop potent and selective PHD finger inhibitors.

Publication metadata

Author(s): Bhushan B, Erdmann A, Zhang Y, Belle R, Johannson C, Oppermann U, Hopkinson RJ, Schofield CJ, Kawamura A

Publication type: Review

Publication status: Published

Journal: Bioorganic and Medicinal Chemistry

Year: 2018

Volume: 26

Issue: 11

Pages: 2984-2991

Print publication date: 15/07/2018

Online publication date: 19/03/2018

Acceptance date: 18/03/2018

ISSN (print): 0968-0896

ISSN (electronic): 1464-3391

Publisher: Elsevier Ltd


DOI: 10.1016/j.bmc.2018.03.030

PubMed id: 29764755