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Synthesis of Carboxamide-Containing Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors Targeting Acute Myeloid Leukemia

Borrello, Maria Teresa, Benelkebir, Hanae, Lee, Adam, Tam, Chak Hin, Shafat, Manar, Rushworth, Stuart A, Bowles, Kristian A, Douglas, Leon, Duriez, Patrick J, Bailey, Sarah, Crabb, Simon J, Packham, Graham and Ganesan, A (2021) Synthesis of Carboxamide-Containing Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors Targeting Acute Myeloid Leukemia. ChemMedChem, 16. pp. 1316-1324. ISSN 1860-7187

Item Type: Article


Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins, and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues with a carboxamide at the 4-position of the aryl ring. These compounds, such as 5 a and 5 b with benzyl and phenethylamide substituents, respectively, had potent sub-micromolar IC50 values for the inhibition of LSD1 as well as cell proliferation in a panel of AML cell lines. The dose-dependent increase in cellular expression levels of H3K4me2, CD86, CD11b and CD14 supported a mechanism involving LSD1 inhibition. The tert-butyl and ethyl carbamate derivatives of these tranylcypromines, although inactive in LSD1 inhibition, were of similar potency in cell-based assays with a more rapid onset of action. This suggests that carbamates can act as metabolically labile tranylcypromine prodrugs with superior pharmacokinetics.

ChemMedChem - 2021 - Teresa Borrello - Synthesis of Carboxamide‐Containing Tranylcypromine Analogues as LSD1 KDM1A .pdf - Published Version
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Depositing User: Teresa Borrello


Item ID: 15951
Identification Number:
ISSN: 1860-7187
Official URL:

Users with ORCIDS

ORCID for Maria Teresa Borrello: ORCID iD

Catalogue record

Date Deposited: 27 Apr 2023 14:35
Last Modified: 30 Apr 2023 16:45


Author: Maria Teresa Borrello ORCID iD
Author: Hanae Benelkebir
Author: Adam Lee
Author: Chak Hin Tam
Author: Manar Shafat
Author: Stuart A Rushworth
Author: Kristian A Bowles
Author: Leon Douglas
Author: Patrick J Duriez
Author: Sarah Bailey
Author: Simon J Crabb
Author: Graham Packham
Author: A Ganesan

University Divisions

Faculty of Health Sciences and Wellbeing


Sciences > Biomedical Sciences
Sciences > Chemistry
Sciences > Pharmacy and Pharmacology

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