Rhodium(III)-Based Inhibitor of the JMJD3-H3K27me3 Interaction and Modulator of the Inflammatory Response

Tian Shu Kang; Chung Nga Ko; Jia Tong Zhang; Chun Wu; Chun Yuen Wong; Dik Lung Ma; Chung Hang Leung

doi:10.1021/acs.inorgchem.8b02256

Rhodium(III)-Based Inhibitor of the JMJD3-H3K27me3 Interaction and Modulator of the Inflammatory Response

Tian Shu Kang, Chung Nga Ko, Jia Tong Zhang, Chun Wu, Chun Yuen Wong, Dik Lung Ma^*, Chung Hang Leung^*

^*Corresponding author for this work

Department of Chemistry

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

13 Citations (Scopus)

Abstract

We describe in this study a rhodium(III) complex 1 as a new JMJD3 inhibitor and proinflammatory mediator. Complex 1 selectively inhibited the demethylation of H3K27me3 over other similar substrates, indicating its selectivity for JMJD3 over other histone demethylases, including JMJD2D and KDM5A. In terms of mechanism, complex 1 inhibited the JMJD3-H3K27me3 interaction in mouse macrophage cells and down-regulated the expression of TNF-α. To our knowledge, complex 1 is the first metal-based inhibitor of JMJD3 activity and only the second class of JMJD3 inhibitor reported overall.

Original language	English
Pages (from-to)	14023-14026
Number of pages	4
Journal	Inorganic Chemistry
Volume	57
Issue number	22
Early online date	30 Oct 2018
DOIs	https://doi.org/10.1021/acs.inorgchem.8b02256
Publication status	Published - 19 Nov 2018

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@article{3be8c6e1b5364cb1aa7df8f748b0e452,

title = "Rhodium(III)-Based Inhibitor of the JMJD3-H3K27me3 Interaction and Modulator of the Inflammatory Response",

abstract = "We describe in this study a rhodium(III) complex 1 as a new JMJD3 inhibitor and proinflammatory mediator. Complex 1 selectively inhibited the demethylation of H3K27me3 over other similar substrates, indicating its selectivity for JMJD3 over other histone demethylases, including JMJD2D and KDM5A. In terms of mechanism, complex 1 inhibited the JMJD3-H3K27me3 interaction in mouse macrophage cells and down-regulated the expression of TNF-α. To our knowledge, complex 1 is the first metal-based inhibitor of JMJD3 activity and only the second class of JMJD3 inhibitor reported overall.",

author = "Kang, {Tian Shu} and Ko, {Chung Nga} and Zhang, {Jia Tong} and Chun Wu and Wong, {Chun Yuen} and Ma, {Dik Lung} and Leung, {Chung Hang}",

note = "Funding Information: This work was supported by Hong Kong Baptist University (Grants FRG2/16-17/007 and FRG2/17-18/003), the Health and Medical Research Fund (Grant HMRF/14150561), the Research Grants Council (Grant HKBU/12301115), the National Natural Science Foundation of China (Grants 21575121, 21775131, and 21628502), the Hong Kong Baptist University Century Club Sponsorship Scheme 2018, the Interdisciplinary Research Matching Scheme (Grants RC-IRMS/15-16/03 and RC-IRMS/16-17/03), Interdisciplinary Research Clusters Matching Scheme (Grant RC-IRCs/17-18/ 03), Innovation and Technology Fund (Grant ITS/260/ 16FX), Collaborative Research Fund (Grant C5026-16G), Matching Proof of Concept Fund (Grant MPCF-001-2017/ 18), SKLEBA and HKBU Strategic Development Fund (Grant SKLP_1718_P04), the Science and Technology Development Fund, Macao SAR (Grant 0072/2018/A2), the University of Macau (Grants MYRG2018-00187-ICMS and MYRG2016-00151-ICMS-QRCM) and the Research Grants Council of Hong Kong SAR (Grants CityU 11228316 and CityU 11207117). Publisher copyright: {\textcopyright} 2018 American Chemical Society",

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doi = "10.1021/acs.inorgchem.8b02256",

language = "English",

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T1 - Rhodium(III)-Based Inhibitor of the JMJD3-H3K27me3 Interaction and Modulator of the Inflammatory Response

AU - Kang, Tian Shu

AU - Ko, Chung Nga

AU - Zhang, Jia Tong

AU - Wu, Chun

AU - Wong, Chun Yuen

AU - Ma, Dik Lung

AU - Leung, Chung Hang

N1 - Funding Information: This work was supported by Hong Kong Baptist University (Grants FRG2/16-17/007 and FRG2/17-18/003), the Health and Medical Research Fund (Grant HMRF/14150561), the Research Grants Council (Grant HKBU/12301115), the National Natural Science Foundation of China (Grants 21575121, 21775131, and 21628502), the Hong Kong Baptist University Century Club Sponsorship Scheme 2018, the Interdisciplinary Research Matching Scheme (Grants RC-IRMS/15-16/03 and RC-IRMS/16-17/03), Interdisciplinary Research Clusters Matching Scheme (Grant RC-IRCs/17-18/ 03), Innovation and Technology Fund (Grant ITS/260/ 16FX), Collaborative Research Fund (Grant C5026-16G), Matching Proof of Concept Fund (Grant MPCF-001-2017/ 18), SKLEBA and HKBU Strategic Development Fund (Grant SKLP_1718_P04), the Science and Technology Development Fund, Macao SAR (Grant 0072/2018/A2), the University of Macau (Grants MYRG2018-00187-ICMS and MYRG2016-00151-ICMS-QRCM) and the Research Grants Council of Hong Kong SAR (Grants CityU 11228316 and CityU 11207117). Publisher copyright: © 2018 American Chemical Society

PY - 2018/11/19

Y1 - 2018/11/19

N2 - We describe in this study a rhodium(III) complex 1 as a new JMJD3 inhibitor and proinflammatory mediator. Complex 1 selectively inhibited the demethylation of H3K27me3 over other similar substrates, indicating its selectivity for JMJD3 over other histone demethylases, including JMJD2D and KDM5A. In terms of mechanism, complex 1 inhibited the JMJD3-H3K27me3 interaction in mouse macrophage cells and down-regulated the expression of TNF-α. To our knowledge, complex 1 is the first metal-based inhibitor of JMJD3 activity and only the second class of JMJD3 inhibitor reported overall.

AB - We describe in this study a rhodium(III) complex 1 as a new JMJD3 inhibitor and proinflammatory mediator. Complex 1 selectively inhibited the demethylation of H3K27me3 over other similar substrates, indicating its selectivity for JMJD3 over other histone demethylases, including JMJD2D and KDM5A. In terms of mechanism, complex 1 inhibited the JMJD3-H3K27me3 interaction in mouse macrophage cells and down-regulated the expression of TNF-α. To our knowledge, complex 1 is the first metal-based inhibitor of JMJD3 activity and only the second class of JMJD3 inhibitor reported overall.

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DO - 10.1021/acs.inorgchem.8b02256

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SN - 0020-1669

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JO - Inorganic Chemistry

JF - Inorganic Chemistry

IS - 22

ER -

Rhodium(III)-Based Inhibitor of the JMJD3-H3K27me3 Interaction and Modulator of the Inflammatory Response

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