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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.

Original publication

DOI

10.1016/j.bmc.2018.03.030

Type

Journal article

Journal

Bioorganic & medicinal chemistry

Publication Date

19/03/2018

Addresses

Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom; Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.