Identification of catechols as histone–lysine demethylase inhibitors

Anders L. Nielsen; Line H. Kristensen; Karen B. Stephansen; Jan B. L. Kristensen; Charlotte Helgstrand; Michael Lees; Paul Cloos; Kristian Helin; Michael Gajhede; Lars Olsen

doi:10.1016/j.febslet.2012.03.001

Identification of catechols as histone–lysine demethylase inhibitors

Anders L. Nielsen
, Line H. Kristensen
, Karen B. Stephansen
, Jan B. L. Kristensen
, Charlotte Helgstrand
, Michael Lees
, Paul Cloos
, Kristian Helin
, Michael Gajhede
, Lars Olsen

Biotech Research & Innovation Centre
University of Copenhagen

Research output: Contribution to journal › Journal article › Research › peer-review

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.

Original language	English
Journal	F E B S Letters
Volume	586
Issue number	8
Pages (from-to)	1190-1194
ISSN	0014-5793
DOIs	https://doi.org/10.1016/j.febslet.2012.03.001
Publication status	Published - 2012
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.febslet.2012.03.001

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@article{fcb0fa3f1aff4bebb7cde3800017bcc7,

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.",

author = "Nielsen, \{Anders L.\} and Kristensen, \{Line H.\} and Stephansen, \{Karen B.\} and Kristensen, \{Jan B. L.\} and Charlotte Helgstrand and Michael Lees and Paul Cloos and Kristian Helin and Michael Gajhede and Lars Olsen",

year = "2012",

doi = "10.1016/j.febslet.2012.03.001",

language = "English",

volume = "586",

pages = "1190--1194",

journal = "F E B S Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "8",

}

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

PY - 2012

Y1 - 2012

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

SN - 0014-5793

VL - 586

SP - 1190

EP - 1194

JO - F E B S Letters

JF - F E B S Letters

IS - 8

ER -

Identification of catechols as histone–lysine demethylase inhibitors

Abstract

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