Issue 12, 2014
From the journal:

MedChemComm

Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor†

Katherine S. England,‡ab   Anthony Tumber,‡ac   Tobias Krojer,a   Giuseppe Scozzafava,ac   Stanley S. Ng,a   Michelle Daniel,a   Aleksandra Szykowska,a   KaHing Che,a   Frank von Delft,ad   Nicola A. Burgess-Brown,a   Akane Kawamura,be   Christopher J. Schofieldb  and  Paul E. Brennan*ac  

* Corresponding authors

a Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Headington OX3 7DQ, UK
E-mail: paul.brennan@sgc.ox.ac.uk

b Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, UK

c Target Discovery Institute, University of Oxford, NDM Research Building, Roosevelt Drive, Oxford, UK

d Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, UK

e Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK

Abstract

A potent inhibitor of the JmjC histone lysine demethylase KDM2A (compound 35, pIC50 7.2) with excellent selectivity over representatives from other KDM subfamilies has been developed; the discovery that a triazolopyridine compound binds to the active site of JmjC KDMs was followed by optimisation of the triazole substituent for KDM2A inhibition and selectivity.

Graphical abstract: Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor

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Article information

DOI
https://doi.org/10.1039/C4MD00291A
Article type
Concise Article
Submitted
04 Jul 2014
Accepted
14 Sep 2014
First published
15 Sep 2014
This article is Open Access
Creative Commons BY license

Med. Chem. Commun., 2014,5, 1879-1886

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Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor

K. S. England, A. Tumber, T. Krojer, G. Scozzafava, S. S. Ng, M. Daniel, A. Szykowska, K. Che, F. von Delft, N. A. Burgess-Brown, A. Kawamura, C. J. Schofield and P. E. Brennan, Med. Chem. Commun., 2014, 5, 1879 DOI: 10.1039/C4MD00291A

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