An Iridium(III) Complex Inhibits JMJD2 Activities and Acts as a Potential Epigenetic Modulator

Li Juan Liu; Lihua Lu; Hai Jing Zhong; Bingyong He; Daniel W. J. Kwong; Dik Lung Ma; Chung Hang Leung

doi:10.1021/acs.jmedchem.5b00375

An Iridium(III) Complex Inhibits JMJD2 Activities and Acts as a Potential Epigenetic Modulator

Li Juan Liu
, Lihua Lu
, Hai Jing Zhong
, Bingyong He
, Daniel W. J. Kwong
, Dik Lung Ma^*
, Chung Hang Leung^*

^*Corresponding author for this work

Department of Chemistry

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

66 Citations (Scopus)

Abstract

A novel iridium(III) complex was synthesized and evaluated for its ability to target JMJD2 enzymatic activity. The iridium(III) complex 1 can inhibit JMJD2 activity and was selective for JMJD2 activity over JARID, JMJD3, and HDAC activities. Moreover, 1 suppressed the trimethylation of the p21 promoter on H3K9me3 and interrupted the JMJD2D-H3K9me3 interactions in human cells, suggesting that it could act as an epigenetic modulator. To our knowledge, 1 represents the first metal-based JMJD2 inhibitor reported in the literature. (Figure Presented).

Original language	English
Pages (from-to)	6697-6703
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	58
Issue number	16
Early online date	11 Aug 2015
DOIs	https://doi.org/10.1021/acs.jmedchem.5b00375
Publication status	Published - 27 Aug 2015

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@article{22ba5625bd5e420fb43b8937fb3dc045,

title = "An Iridium(III) Complex Inhibits JMJD2 Activities and Acts as a Potential Epigenetic Modulator",

abstract = "A novel iridium(III) complex was synthesized and evaluated for its ability to target JMJD2 enzymatic activity. The iridium(III) complex 1 can inhibit JMJD2 activity and was selective for JMJD2 activity over JARID, JMJD3, and HDAC activities. Moreover, 1 suppressed the trimethylation of the p21 promoter on H3K9me3 and interrupted the JMJD2D-H3K9me3 interactions in human cells, suggesting that it could act as an epigenetic modulator. To our knowledge, 1 represents the first metal-based JMJD2 inhibitor reported in the literature. (Figure Presented).",

author = "Liu, \{Li Juan\} and Lihua Lu and Zhong, \{Hai Jing\} and Bingyong He and Kwong, \{Daniel W. J.\} and Ma, \{Dik Lung\} and Leung, \{Chung Hang\}",

note = "Funding information: This work is supported by Hong Kong Baptist University (FRG2/14-15/004), Centre for Cancer and Inflammation Research, School of Chinese Medicine (CCIR-SCM, HKBU), the Health and Medical Research Fund (HMRF/13121482 and HMRF/14130522), the Research Grants Council (HKBU/201811, HKBU/204612, and HKBU/201913), the French National Research Agency/Research Grants Council Joint Research Scheme (A-HKBU201/12 - Oligoswitch), Interdisciplinary Research Matching Scheme (RC-IRMS/14-15/06), the Science and Technology Development Fund, Macao SAR (103/2012/A3 and 098/2014/A2), and the University of Macau (MYRG091(Y3-L2)-ICMS12-LCH, MYRG2015-00137-ICMS-QRCM, and MRG023/LCH/2013/ICMS). Publisher copyright: {\textcopyright} 2015 American Chemical Society",

year = "2015",

month = aug,

day = "27",

doi = "10.1021/acs.jmedchem.5b00375",

language = "English",

volume = "58",

pages = "6697--6703",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "16",

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T1 - An Iridium(III) Complex Inhibits JMJD2 Activities and Acts as a Potential Epigenetic Modulator

AU - Liu, Li Juan

AU - Lu, Lihua

AU - Zhong, Hai Jing

AU - He, Bingyong

AU - Kwong, Daniel W. J.

AU - Ma, Dik Lung

AU - Leung, Chung Hang

N1 - Funding information: This work is supported by Hong Kong Baptist University (FRG2/14-15/004), Centre for Cancer and Inflammation Research, School of Chinese Medicine (CCIR-SCM, HKBU), the Health and Medical Research Fund (HMRF/13121482 and HMRF/14130522), the Research Grants Council (HKBU/201811, HKBU/204612, and HKBU/201913), the French National Research Agency/Research Grants Council Joint Research Scheme (A-HKBU201/12 - Oligoswitch), Interdisciplinary Research Matching Scheme (RC-IRMS/14-15/06), the Science and Technology Development Fund, Macao SAR (103/2012/A3 and 098/2014/A2), and the University of Macau (MYRG091(Y3-L2)-ICMS12-LCH, MYRG2015-00137-ICMS-QRCM, and MRG023/LCH/2013/ICMS). Publisher copyright: © 2015 American Chemical Society

PY - 2015/8/27

Y1 - 2015/8/27

N2 - A novel iridium(III) complex was synthesized and evaluated for its ability to target JMJD2 enzymatic activity. The iridium(III) complex 1 can inhibit JMJD2 activity and was selective for JMJD2 activity over JARID, JMJD3, and HDAC activities. Moreover, 1 suppressed the trimethylation of the p21 promoter on H3K9me3 and interrupted the JMJD2D-H3K9me3 interactions in human cells, suggesting that it could act as an epigenetic modulator. To our knowledge, 1 represents the first metal-based JMJD2 inhibitor reported in the literature. (Figure Presented).

AB - A novel iridium(III) complex was synthesized and evaluated for its ability to target JMJD2 enzymatic activity. The iridium(III) complex 1 can inhibit JMJD2 activity and was selective for JMJD2 activity over JARID, JMJD3, and HDAC activities. Moreover, 1 suppressed the trimethylation of the p21 promoter on H3K9me3 and interrupted the JMJD2D-H3K9me3 interactions in human cells, suggesting that it could act as an epigenetic modulator. To our knowledge, 1 represents the first metal-based JMJD2 inhibitor reported in the literature. (Figure Presented).

UR - https://www.scopus.com/pages/publications/84940539379

U2 - 10.1021/acs.jmedchem.5b00375

DO - 10.1021/acs.jmedchem.5b00375

M3 - Journal article

C2 - 26225543

AN - SCOPUS:84940539379

SN - 0022-2623

VL - 58

SP - 6697

EP - 6703

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 16

ER -

An Iridium(III) Complex Inhibits JMJD2 Activities and Acts as a Potential Epigenetic Modulator

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