title: Histone Lysine Demethylase Inhibitors.
abstract: The dynamic regulation of covalent modifications to histones is essential for maintaining genomic integrity and cell identity and is often compromised in cancer. Aberrant expression of histone lysine demethylases has been documented in many types of blood and solid tumors, and thus demethylases represent promising therapeutic targets. Recent advances in high-throughput chemical screening, structure-based drug design, and structure-activity relationship studies have improved both the specificity and the in vivo efficacy of demethylase inhibitors. This review will briefly outline the connection between demethylases and cancer and will provide a comprehensive overview of the structure, specificity, and utility of currently available demethylase inhibitors. To date, a select group of demethylase inhibitors is being evaluated in clinical trials, and additional compounds may soon follow from the bench to the bedside.
authors.affiliation: Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Jambhekar
authors.affiliation: Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.|Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Anastas
authors.affiliation: Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.|Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D056466:Histone Demethylases