|
|||||
|
|
Investigations on small molecule inhibitors targeting the histone H3K4 tri-methyllysine binding PHD-finger of JmjC histone demethylases |
|
| Authors: | Bhaskar Bhushan Alexandre Erdmann Yijia Zhang Roman Belle Catrine Johannson Udo Oppermann Richard J Hopkinson Christopher J Schofield Akane Kawamura |
| Institution: | 1. Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom;2. 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;3. Botnar Research Centre, NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, United Kingdom |
| Abstract: | 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. |
| Keywords: | Epigenetics PHD-finger inhibitor Plant Homeodomain JmjC-KDMs Histone demethylases |
| 本文献已被 ScienceDirect 等数据库收录！ | |