- 18F-Labeled PET Probe Targeting Enhancer of Zeste Homologue 2 (EZH2) for Cancer Imaging
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The enzyme enhancer of zeste homologue 2 (EZH2) plays a catalytic role in histone methylation (H3K27me3), one of the epigenetic modifications that is dysregulated in cancer. The development of a positron emission tomography (PET) imaging agent targeting E
- Yu, Lihai,Despotovic, Nikola,Kovacs, Michael S.,Pin, Christopher L.,Luyt, Leonard G.
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supporting information
p. 334 - 340
(2019/03/11)
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- Structure-activity relationship studies for enhancer of zeste homologue 2 (EZH2) and enhancer of zeste homologue 1 (EZH1) inhibitors
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EZH2 or EZH1 (enhancer of zeste homologue 2 or 1) is the catalytic subunit of polycomb repressive complex 2 (PRC2) that catalyzes methylation of histone H3 lysine 27 (H3K27). PRC2 hyperactivity and/or hypertrimethylation of H3K27 are associated with numerous human cancers, therefore inhibition of PRC2 complex has emerged as a promising therapeutic approach. Recent studies have shown that EZH2 and EZH1 are not functionally redundant and inhibition of both EZH2 and EZH1 is necessary to block the progression of certain cancers such as mixed-lineage leukemia (MLL)-rearranged leukemias. Despite the significant advances in discovery of EZH2 inhibitors, there has not been a systematic structure-activity relationship (SAR) study to investigate the selectivity between EZH2 and EZH1 inhibition. Here, we report our SAR studies that focus on modifications to various regions of the EZH2/1 inhibitor UNC1999 (5) to investigate the impact of the structural changes on EZH2 and EZH1 inhibition and selectivity.
- Yang, Xiaobao,Li, Fengling,Konze, Kyle D.,Meslamani, Jamel,Ma, Anqi,Brown, Peter J.,Zhou, Ming-Ming,Arrowsmith, Cheryl H.,ümit Kaniskan,Vedadi, Masoud,Jin, Jian
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supporting information
p. 7617 - 7633
(2016/09/04)
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- Identification of potent, selective, cell-Active inhibitors of the histone lysine methyltransferase EZH2
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The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-Active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.
- Verma, Sharad K.,Tian, Xinrong,Lafrance, Louis V.,Duquenne, Céline,Suarez, Dominic P.,Newlander, Kenneth A.,Romeril, Stuart P.,Burgess, Joelle L.,Grant, Seth W.,Brackley, James A.,Graves, Alan P.,Scherzer, Daryl A.,Shu, Art,Thompson, Christine,Ott, Heidi M.,Van Aller, Glenn S.,MacHutta, Carl A.,Diaz, Elsie,Jiang, Yong,Johnson, Neil W.,Knight, Steven D.,Kruger, Ryan G.,McCabe, Michael T.,Dhanak, Dashyant,Tummino, Peter J.,Creasy, Caretha L.,Miller, William H.
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supporting information
p. 1091 - 1096
(2013/02/23)
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- INDAZOLES
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Herein are disclosed indazoles of formula (I) where the various groups are defined herein, and which are useful for treating cancer.
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Page/Page column 40
(2011/11/30)
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