Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A). Issue 10 (15th May 2017)

• Record Type: Journal Article
• Authors: Borrello, Maria Teresa; Schinor, Benjamin; Bartels, Katharina; Benelkebir, Hanae; Pereira, Sara; Al-Jamal, Wafa T.; Douglas, Leon; Duriez, Patrick J.; Packham, Graham; Haufe, Günter; Ganesan, A.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 10(2017)
• Page Start: 2099
• Page End: 2101
• Publication Date: 2017-05-15
• Subjects: Organofluorine compounds -- Epigenetics -- FAD-dependent enzymes -- Lysine demethylase -- Mechanism based inhibitors; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.03.081
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.