title: Identification of catechols as histone-lysine demethylase inhibitors.
abstract: Identification of inhibitors of histone-lysine demethylase (HDM) enzymes is important because of their involvement in the development of cancer. An ELISA-based assay was developed for identification of inhibitors of the HDM KDM4C in a natural products library. Based on one of the hits with affinity in the low μM range (1, a catechol), a subset of structurally related compounds was selected and tested against a panel of HDMs. In this subset, two inhibitors (2 and 10) had comparable affinities towards KDM4C and KDM6A but no effect on PHF8. One inhibitor restored H3K9me3 levels in KDM4C transfected U2-OS cells.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders L
authors.initials: AL
authors.lastname: Nielsen
authors.forename: Line H
authors.initials: LH
authors.lastname: Kristensen
authors.forename: Karen B
authors.initials: KB
authors.lastname: Stephansen
authors.forename: Jan B L
authors.initials: JB
authors.lastname: Kristensen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Helgstrand
authors.forename: Michael
authors.initials: M
authors.lastname: Lees
authors.forename: Paul
authors.initials: P
authors.lastname: Cloos
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
authors.forename: Michael
authors.initials: M
authors.lastname: Gajhede
authors.forename: Lars
authors.initials: L
authors.lastname: Olsen
mesh_terms: D002396:Catechols / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D014407:Tumor Cells, Cultured
chemical_list: D002396:Catechols; D056466:Histone Demethylases