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


Journal

ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013

Informations de publication

Date de publication:
20 04 2021
Historique:
revised: 18 12 2020
received: 22 09 2020
pubmed: 4 2 2021
medline: 12 1 2022
entrez: 3 2 2021
Statut: ppublish

Résumé

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 IC

Identifiants

pubmed: 33533576
doi: 10.1002/cmdc.202000754
doi:

Substances chimiques

Antineoplastic Agents 0
Enzyme Inhibitors 0
Tranylcypromine 3E3V44J4Z9
Histone Demethylases EC 1.14.11.-
KDM1A protein, human EC 1.5.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1316-1324

Informations de copyright

© 2021 Wiley-VCH GmbH.

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Auteurs

Maria Teresa Borrello (M)

School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, UK.

Hanae Benelkebir (H)

School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, UK.

Adam Lee (A)

School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, UK.

Chak Hin Tam (C)

School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, UK.

Manar Shafat (M)

Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK.

Stuart A Rushworth (SA)

Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK.

Kristian M Bowles (KM)

Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK.

Leon Douglas (L)

Protein Core Facility and Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicines Centre University of Southampton Southampton General Hospital, Southampton, SO16 6YD, UK.

Patrick J Duriez (PJ)

Protein Core Facility and Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicines Centre University of Southampton Southampton General Hospital, Southampton, SO16 6YD, UK.

Sarah Bailey (S)

Protein Core Facility and Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicines Centre University of Southampton Southampton General Hospital, Southampton, SO16 6YD, UK.

Simon J Crabb (SJ)

Protein Core Facility and Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicines Centre University of Southampton Southampton General Hospital, Southampton, SO16 6YD, UK.

Graham Packham (G)

Protein Core Facility and Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicines Centre University of Southampton Southampton General Hospital, Southampton, SO16 6YD, UK.

A Ganesan (A)

School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, UK.

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Classifications MeSH