Identification of catechols as histone-lysine demethylase inhibitors

TY - JOUR

T1 - Identification of catechols as histone-lysine demethylase inhibitors

AU - Nielsen, Anders L

AU - Kristensen, Line H

AU - Stephansen, Karen B

AU - Kristensen, Jan B L

AU - Helgstrand, Charlotte

AU - Lees, Michael

AU - Cloos, Paul

AU - Helin, Kristian

AU - Gajhede, Michael

AU - Olsen, Lars

N1 - Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PY - 2012/4/24

Y1 - 2012/4/24

N2 - 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.

AB - 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.

U2 - 10.1016/j.febslet.2012.03.001

DO - 10.1016/j.febslet.2012.03.001

M3 - Journal article

C2 - 22575654

SN - 0014-5793

VL - 586

SP - 1190

EP - 1194

JO - F E B S Letters

JF - F E B S Letters

IS - 8

ER -