Deferiprone: Pan-selective Histone Lysine Demethylase Inhibition Activity and Structure Activity Relationship Study

• Published in: Scientific reports Vol. 9; no. 1; p. 4802
• Main Authors: Khodaverdian, Verjine, Tapadar, Subhasish, MacDonald, Ian A., Xu, Yuan, Ho, Po-Yi, Bridges, Allison, Rajpurohit, Pragya, Sanghani, Bhakti A., Fan, Yuhong, Thangaraju, Muthusamy, Hathaway, Nathaniel A., Oyelere, Adegboyega K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.03.2019; Nature Publishing Group
• Subjects: 631/154/309/2420; 631/67/1347; 82; Animal models; Animals; Antitumor agents; Breast cancer; Catalytic Domain - drug effects; Cell Line, Tumor; Chelates; Chelation; Chromatin; Cytotoxicity; Deferiprone - pharmacology; Demethylation; DNA Methylation - drug effects; Enzyme Assays; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Gene silencing; Histone Code - drug effects; Histone Demethylases - antagonists & inhibitors; Histone Demethylases - chemistry; Histones - metabolism; Humanities and Social Sciences; Humans; Inhibitory Concentration 50; Iron; Lysine; Mice; Molecular Docking Simulation; multidisciplinary; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; Recombinant Proteins - metabolism; Reductase; Ribonucleotide reductase; Science; Science (multidisciplinary); Structure-Activity Relationship; Tumor cell lines; Xenograft Model Antitumor Assays; Xenografts

Deferiprone (DFP) is a hydroxypyridinone-derived iron chelator currently in clinical use for iron chelation therapy. DFP has also been known to elicit antiproliferative activities, yet the mechanism of this effect has remained elusive. We herein report that DFP chelates the Fe 2+ ion at the active s...