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

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Sun K,Peng JD,Suo FZ,Zhang T,Fu YD,Zheng YC,Liu HM

doi

10.1016/j.bmcl.2017.10.003

subject

Has Abstract

pub_date

2017-11-15 00:00:00

pages

5036-5039

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30977-0

journal_volume

27

pub_type

杂志文章

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