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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macao P. R. China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Hong Kong Baptist University , Kowloon Tong, Hong Kong P. R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macao P. R. China.
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Zhong
authors.affiliation: Department of Chemistry, Hong Kong Baptist University , Kowloon Tong, Hong Kong P. R. China.
authors.forename: Bingyong
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Chemistry, Hong Kong Baptist University , Kowloon Tong, Hong Kong P. R. China.
authors.forename: Daniel W J
authors.initials: DW
authors.lastname: Kwong
authors.affiliation: Department of Chemistry, Hong Kong Baptist University , Kowloon Tong, Hong Kong P. R. China.
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macao P. R. China.
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D007501:Iron / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D006657:Histones; D009942:Organometallic Compounds; D007495:Iridium; D007501:Iron; D056484:Jumonji Domain-Containing Histone Demethylases; C521694:KDM4D protein, human