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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on the storage and integration of epigenetic drug datasets that were obtained from laboratory experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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A Selective Phenelzine Analog Inhibitor of Histone Demethylase LSD1

Drug Name:bizine
Drug Category:HDMi
Sample Type:human LNCaP cells
Condition:prostate cancer
Experiment Type:Genome binding/occupancy profiling by high throughput sequencing
Experiment Platform:GPL11154Illumina HiSeq
Description:Lysine-specific demethylase 1 (LSD1) is an epigenetic enzyme that oxidatively cleaves methyl groups from monomethyl and dimethyl Lys4 of histone H3 (H3K4Me1, H3K4Me2) and can contribute to gene silencing. This study describes the design and synthesis of analogues of a monoamine oxidase antidepressant, phenelzine, and their LSD1 inhibitory properties. A novel phenelzine analogue (bizine) containing a phenyl-butyrylamide appendage was shown to be a potent LSD1 inhibitor in vitro and was selective versus monoamine oxidases A/B and the LSD1 homologue, LSD2. Bizine was found to be effective at modulating bulk histone methylation in cancer cells, and ChIP-seq experiments revealed a statistically significant overlap in the H3K4 methylation pattern of genes affected by bizine and those altered in LSD1-/- cells. Treatment of two cancer cell lines, LNCaP and H460, with bizine conferred a reduction in proliferation rate, and bizine showed additive to synergistic effects on cell growth when used in combination with two out of five HDAC inhibitors tested. Moreover, neurons exposed to oxidative stress were protected by the presence of bizine, suggesting potential applications in neurodegenerative disease.
PubmedID:24707965
Citation:Prusevich P;Kalin JH; Ming SA;Basso M;Givens J;Li X;Hu J;Taylor MS;Cieniewicz AM;Hsiao PY;Huang R;Roberson H;Adejola N;Avery LB;Casero RA Jr;Taverna SD;Qian J;Tackett AJ;Ratan RR;McDonald OG;Feinberg AP;Cole PA. A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Biol 2014 Jun 20;9(6):1284-93.
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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on integrating epigenetic drug studies based Omics data from high through experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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©2016 Group of Computational Epigenomics and Bioinformatics, College of Life Science, Jilin Normal University, China

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