Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A)

Borrello, Maria Teresa, Schinor, Benjamin, Bartels, Katharina, Benelkebir, Hanae, Pereira, Sara, Al-Jamal, Wafa T., Douglas, Leon, Duriez, Patrick J., Packham, Graham, Haufe, Günter and Ganesan, A. (2017) Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A). Bioorganic & Medicinal Chemistry Letters, 27 (10). 2099–2101. ISSN 0960-894X

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Abstract

We report a series of tranylcypromine analogues containing a fluorine in the cyclopropyl ring. A number of compounds with additional m- or p- substitution of the aryl ring were micromolar inhibitors of the LSD1 enzyme. In cellular assays, the compounds inhibited the proliferation of acute myeloid leukemia cell lines. Increased levels of the biomarkers H3K4me2 and CD86 were consistent with LSD1 target engagement.

Item Type: Article
Uncontrolled Keywords: organofluorine compounds,epigenetics,fad-dependent enzymes,lysine demethylase,mechanism based inhibitors
Faculty \ School: Faculty of Science
Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: Pure Connector
Date Deposited: 06 Apr 2017 06:59
Last Modified: 22 Jul 2020 01:29
URI: https://ueaeprints.uea.ac.uk/id/eprint/63177
DOI: 10.1016/j.bmcl.2017.03.081

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