Discovery of tranylcypromine analogs with an acylhydrazone substituent as LSD1 inactivators: Design, synthesis and their biological evaluation

[Display omitted] Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression, has been reported to be up-regulated and involved in numbers of solid malignant tumors. In this study, we identified a...

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Published in:Bioorganic & medicinal chemistry letters 2017-11, Vol.27 (22), p.5036-5039
Main Authors: Sun, Kai, Peng, Jia-Di, Suo, Feng-Zhi, Zhang, Ting, Fu, Yun-Dong, Zheng, Yi-Chao, Liu, Hong-Min
Format: Article
Language:English
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Summary:[Display omitted] Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression, has been reported to be up-regulated and involved in numbers of solid malignant tumors. In this study, we identified a series of phenylalanyl hydrazones based LSD1 inhibitors, and the most potent one, compound 4q, can inactivate LSD1 with IC50 = 91.83 nM. In cellular level, compound 4q can induce the accumulation of CD86 as well as H3K4me2, and inhibit gastric cancer cell proliferation by inactivating LSD1. Our findings indicated that compound 4q may serve as a potential leading compound to target LSD1 overexpressed gastric cancer.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2017.10.003