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

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

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.

Journal Article
2099-2101
Borrello, Maria Teresa
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Schinor, Benjamin
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Bartels, Katharina
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Benelkebir, Hanae
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Pereira, Sara
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Al-Jamal, Wafa T.
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Douglas, Leon
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Duriez, Patrick J.
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Packham, Graham
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Haufe, Günter
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Ganesan, Anusha
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Borrello, Maria Teresa
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Schinor, Benjamin
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Bartels, Katharina
36ac0559-4a3f-413c-b3eb-8711eadc14ab
Benelkebir, Hanae
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Pereira, Sara
29f41370-3f32-4599-8eac-bef227246eb7
Al-Jamal, Wafa T.
12867ec2-bc37-49d9-a48e-ef65fff573c0
Douglas, Leon
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Duriez, Patrick J.
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Packham, Graham
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Haufe, Günter
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Ganesan, Anusha
8453180c-2d4a-4415-b675-192df230a7b9

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, Anusha (2017) Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A). Bioorganic & Medicinal Chemistry Letters, 27 (10), 2099-2101. (doi:10.1016/j.bmcl.2017.03.081).

Record type: Article

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.

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BorrelloBMCL2017RevisedManuscript - Accepted Manuscript
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More information

Accepted/In Press date: 25 March 2017
e-pub ahead of print date: 29 March 2017
Published date: 15 May 2017
Keywords: Journal Article

Identifiers

Local EPrints ID: 413054
URI: http://eprints.soton.ac.uk/id/eprint/413054
PURE UUID: a0db558e-6f95-4ea7-914a-942ba4ab27e6
ORCID for Patrick J. Duriez: ORCID iD orcid.org/0000-0003-1814-2552
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

Catalogue record

Date deposited: 14 Aug 2017 16:30
Last modified: 16 Mar 2024 05:24

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Contributors

Author: Maria Teresa Borrello
Author: Benjamin Schinor
Author: Katharina Bartels
Author: Hanae Benelkebir
Author: Sara Pereira
Author: Wafa T. Al-Jamal
Author: Leon Douglas
Author: Patrick J. Duriez ORCID iD
Author: Graham Packham ORCID iD
Author: Günter Haufe
Author: Anusha Ganesan

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