Inhibition of JMJD6 by 2-Oxoglutarate Mimics

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.

Automated summary

This study discusses the inhibition of human 2-oxoglutarate dependent oxygenase JMJD6, a cancer target, by 2-oxoglutarate mimics/competitors. NMR and mass spectrometry were used to monitor inhibitor binding and JMJD6-catalyzed lysine hydroxylation. Clinically applied prolyl hydroxylase inhibitors were found to also inhibit JMJD6, suggesting the potential for developing selective inhibitors for human oxygenases.