Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor.
England KS., Tumber A., Krojer T., Scozzafava G., Ng SS., Daniel M., Szykowska A., Che K., von Delft F., Burgess-Brown NA., Kawamura A., Schofield CJ., Brennan PE.
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.