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.
Keywords:
Epigenetics; FAD-dependent enzymes; Lysine demethylase; Mechanism based inhibitors; Organofluorine compounds.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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B7-2 Antigen / metabolism
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Biomarkers / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / toxicity
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Halogenation
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Histone Demethylases / antagonists & inhibitors*
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Histone Demethylases / metabolism
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Histones / metabolism
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Humans
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Inhibitory Concentration 50
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Tranylcypromine / analogs & derivatives*
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Tranylcypromine / chemical synthesis
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Tranylcypromine / toxicity
Substances
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B7-2 Antigen
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Biomarkers
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Enzyme Inhibitors
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Histones
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Tranylcypromine
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Histone Demethylases
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KDM1A protein, human