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

Maria Teresa Borrello; Benjamin Schinor; Katharina Bartels; Hanae Benelkebir; Sara Pereira; Wafa T. Al-Jamal; Leon Douglas; Patrick J. Duriez; Graham Packham; Günter Haufe; A. Ganesan

doi:10.1016/j.bmcl.2017.03.081

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

Maria Teresa Borrello, Benjamin Schinor, Katharina Bartels, Hanae Benelkebir, Sara Pereira, Wafa T. Al-Jamal, Leon Douglas, Patrick J. Duriez, Graham Packham, Günter Haufe, A. Ganesan

Faculty of Science

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	2099–2101
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	27
Issue number	10
Early online date	29 Mar 2017
DOIs	https://doi.org/10.1016/j.bmcl.2017.03.081
Publication status	Published - 15 May 2017

Keywords

Organofluorine compounds
Epigenetics
FAD-dependent enzymes
Lysine demethylase
Mechanism based inhibitors

Access to Document

10.1016/j.bmcl.2017.03.081

Accepted manuscriptAccepted author manuscript, 391 KBLicence: CC BY-NC-ND

http://linkinghub.elsevier.com/retrieve/pii/S0960894X17303311

A. Ganesan
- A.Ganesanuea.acuk
- School of Chemistry, Pharmacy and Pharmacology - Professor in Chemical Biology
Person: Academic, Teaching & Research

Engineering Multi-Functional Nanomaterials to Treat Metastatic Cancer.
Al-Jamal, W.
Engineering and Physical Sciences Research Council
18/05/15 → 21/07/17
Project: Research

Cite this

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

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 = "Organofluorine compounds, Epigenetics, FAD-dependent enzymes, Lysine demethylase, Mechanism based inhibitors",

author = "Borrello, {Maria Teresa} and Benjamin Schinor and Katharina Bartels and Hanae Benelkebir and Sara Pereira and Al-Jamal, {Wafa T.} and Leon Douglas and Duriez, {Patrick J.} and Graham Packham and G{\"u}nter Haufe and A. Ganesan",

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doi = "10.1016/j.bmcl.2017.03.081",

language = "English",

volume = "27",

pages = "2099–2101",

journal = "Bioorganic & Medicinal Chemistry Letters",

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TY - JOUR

T1 - Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A)

AU - Borrello, Maria Teresa

AU - Schinor, Benjamin

AU - Bartels, Katharina

AU - Benelkebir, Hanae

AU - Pereira, Sara

AU - Al-Jamal, Wafa T.

AU - Douglas, Leon

AU - Duriez, Patrick J.

AU - Packham, Graham

AU - Haufe, Günter

AU - Ganesan, A.

PY - 2017/5/15

Y1 - 2017/5/15

N2 - 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.

AB - 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.

KW - Organofluorine compounds

KW - Epigenetics

KW - FAD-dependent enzymes

KW - Lysine demethylase

KW - Mechanism based inhibitors

U2 - 10.1016/j.bmcl.2017.03.081

DO - 10.1016/j.bmcl.2017.03.081

M3 - Article

VL - 27

SP - 2099

EP - 2101

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 10

ER -

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

Abstract

Keywords

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Profiles

A. Ganesan

Projects

Engineering Multi-Functional Nanomaterials to Treat Metastatic Cancer.

Cite this