Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

Ulrike Leurs; Rasmus P Clausen; Jesper L Kristensen; Brian Lohse

doi:10.1016/j.bmcl.2012.07.091

Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

Ulrike Leurs, Rasmus P Clausen, Jesper L Kristensen, Brian Lohse

15 Citationer (Scopus)

Abstract

The human histone demethylases of the KDM4 (JMJD2) family have been associated to diseases such as prostate and breast cancer, as well as X-linked mental retardation. Therefore, these enzymes are considered oncogenes and their selective inhibition might be a possible therapeutic approach to treat cancer. Here we describe a heterocyclic ring system library screened against the histone demethylase KDM4C (JMJD2C) in the search for novel inhibitory scaffolds. A 4-hydroxypyrazole scaffold was identified as an inhibitor of KDM4C; this scaffold could be employed in the further development of novel therapeutics, as well as for the elucidation of the biological roles of KDM4C on epigenetic regulation.

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	22
Udgave nummer	18
Sider (fra-til)	5811-3
Antal sider	3
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2012.07.091
Status	Udgivet - 15 sep. 2012

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10.1016/j.bmcl.2012.07.091

My PhD project
Leurs, U. (Deltager)
1 aug. 2011 → 31 jul. 2014
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Citationsformater

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abstract = "The human histone demethylases of the KDM4 (JMJD2) family have been associated to diseases such as prostate and breast cancer, as well as X-linked mental retardation. Therefore, these enzymes are considered oncogenes and their selective inhibition might be a possible therapeutic approach to treat cancer. Here we describe a heterocyclic ring system library screened against the histone demethylase KDM4C (JMJD2C) in the search for novel inhibitory scaffolds. A 4-hydroxypyrazole scaffold was identified as an inhibitor of KDM4C; this scaffold could be employed in the further development of novel therapeutics, as well as for the elucidation of the biological roles of KDM4C on epigenetic regulation.",

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author = "Ulrike Leurs and Clausen, {Rasmus P} and Kristensen, {Jesper L} and Brian Lohse",

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AU - Leurs, Ulrike

AU - Clausen, Rasmus P

AU - Kristensen, Jesper L

AU - Lohse, Brian

PY - 2012/9/15

Y1 - 2012/9/15

N2 - The human histone demethylases of the KDM4 (JMJD2) family have been associated to diseases such as prostate and breast cancer, as well as X-linked mental retardation. Therefore, these enzymes are considered oncogenes and their selective inhibition might be a possible therapeutic approach to treat cancer. Here we describe a heterocyclic ring system library screened against the histone demethylase KDM4C (JMJD2C) in the search for novel inhibitory scaffolds. A 4-hydroxypyrazole scaffold was identified as an inhibitor of KDM4C; this scaffold could be employed in the further development of novel therapeutics, as well as for the elucidation of the biological roles of KDM4C on epigenetic regulation.

AB - The human histone demethylases of the KDM4 (JMJD2) family have been associated to diseases such as prostate and breast cancer, as well as X-linked mental retardation. Therefore, these enzymes are considered oncogenes and their selective inhibition might be a possible therapeutic approach to treat cancer. Here we describe a heterocyclic ring system library screened against the histone demethylase KDM4C (JMJD2C) in the search for novel inhibitory scaffolds. A 4-hydroxypyrazole scaffold was identified as an inhibitor of KDM4C; this scaffold could be employed in the further development of novel therapeutics, as well as for the elucidation of the biological roles of KDM4C on epigenetic regulation.

KW - Dose-Response Relationship, Drug

KW - Drug Design

KW - Enzyme Inhibitors

KW - Humans

KW - Jumonji Domain-Containing Histone Demethylases

KW - Molecular Structure

KW - Pyrazoles

KW - Small Molecule Libraries

KW - Structure-Activity Relationship

U2 - 10.1016/j.bmcl.2012.07.091

DO - 10.1016/j.bmcl.2012.07.091

M3 - Journal article

C2 - 22917519

SN - 0960-894X

VL - 22

SP - 5811

EP - 5813

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 18

ER -

Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

Abstract

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