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 Citations (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.

Original language	English
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	22
Issue number	18
Pages (from-to)	5811-3
Number of pages	3
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2012.07.091
Publication status	Published - 15 Sept 2012

Keywords

Dose-Response Relationship, Drug
Drug Design
Enzyme Inhibitors
Humans
Jumonji Domain-Containing Histone Demethylases
Molecular Structure
Pyrazoles
Small Molecule Libraries
Structure-Activity Relationship

UN SDGs

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

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10.1016/j.bmcl.2012.07.091

My PhD project
Leurs, U. (Participant)
1 Aug 2011 → 31 Jul 2014
Activity: Other activity types › Other (prizes, external teaching and other activities) - Other

Cite this

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title = "Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)",

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",

year = "2012",

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doi = "10.1016/j.bmcl.2012.07.091",

language = "English",

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T1 - Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

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

Keywords

UN SDGs

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Activities

My PhD project

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