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; Edmond 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, Edmond Dik Lung MA^*, Chung Hang Leung

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

47 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
DOIs	https://doi.org/10.1021/acs.jmedchem.5b00375
Publication status	Published - 27 Aug 2015

Scopus Subject Areas

Molecular Medicine
Drug Discovery

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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, {Edmond Dik Lung} and Leung, {Chung Hang}",

year = "2015",

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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, Edmond Dik Lung

AU - Leung, Chung Hang

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).

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VL - 58

SP - 6697

EP - 6703

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 16

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

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