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 07:59
    Last Modified: 09 Apr 2019 12:06
    URI: https://ueaeprints.uea.ac.uk/id/eprint/63177
    DOI: 10.1016/j.bmcl.2017.03.081

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