Investigations on small molecule inhibitors targeting the histone H3K4 tri-methyllysine binding PHD-finger of JmjC histone demethylases. Issue 11 (15th July 2018)

• Record Type: Journal Article
• Authors: Bhushan, Bhaskar; Erdmann, Alexandre; Zhang, Yijia; Belle, Roman; Johannson, Catrine; Oppermann, Udo; Hopkinson, Richard J.; Schofield, Christopher J.; Kawamura, Akane
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 11(2018)
• Page Start: 2984
• Page End: 2991
• Publication Date: 2018-07-15
• Subjects: Epigenetics -- PHD-finger inhibitor -- Plant Homeodomain -- JmjC-KDMs -- Histone demethylases; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.03.030
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.