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. ORCID: https://orcid.org/0000-0003-4862-7999 (2017) Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A). Bioorganic & Medicinal Chemistry Letters, 27 (10). 2099–2101. ISSN 0960-894X

[thumbnail of Accepted manuscript]
Preview
PDF (Accepted manuscript) - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (400kB) | Preview

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
UEA Research Groups: Faculty of Science > Research Groups > Drug Delivery and Pharmaceutical Materials (former - to 2017)
Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017)
Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
Related URLs:
Depositing User: Pure Connector
Date Deposited: 06 Apr 2017 06:59
Last Modified: 22 Oct 2022 02:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/63177
DOI: 10.1016/j.bmcl.2017.03.081

Actions (login required)

View Item View Item