Inhibition of JMJD6 by 2-Oxoglutarate Mimics

Abstract

Studies on the inhibition of the human 2-oxoglutarate dependent oxygenase JMJD6, which is a cancer target, by 2-oxoglutarate mimics / competitors, including human drugs, drug candidates, and metabolites relevant to cancer are described. JMJD6 assays employed NMR to monitor inhibitor binding and use of mass spectrometry to monitor JMJD6-catalysed lysine hydroxylation. Notably, some clinically applied prolyl hydroxylase inhibitors also inhibit JMJD6. The results will help enable the development of inhibitors selective for human oxygenases, including JMJD6.