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

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.

SUBMITTER: England KS

PROVIDER: S-EPMC4678576 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

England Katherine S KS Tumber Anthony A Krojer Tobias T Scozzafava Giuseppe G Ng Stanley S SS Daniel Michelle M Szykowska Aleksandra A Che KaHing K von Delft Frank F Burgess-Brown Nicola A NA Kawamura Akane A Schofield Christopher J CJ Brennan Paul E PE

MedChemComm 20141201 12

A potent inhibitor of the JmjC histone lysine demethylase KDM2A (compound <b>35</b>, pIC<sub>50</sub> 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. ...[more]

PMID: 26682034

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