Histone demethylases (KDMs) catalyze the removal of methyl groups from histone lysine residues and function in the regulation of gene expression. Members of the KDM5 demethylase family are amplified and/or over expressed in a number of human cancers, and both proteins have been described as co-regulators of established oncogenes. In addition, KDM5A and KDM5B were identified as mediators of resistance to targeted and cytotoxic agents. KDM5 enzymes represent interesting oncology candidate targets, however, selective KDM5 inhibitors have not yet been discovered.
Our paper reporting the discovery of novel KDM5 histone demethylase inhibitors and their application in cancer cell models of drug tolerance, is available on Monday, May 23rd at 11AM EST, in the journal Nature Chemical Biology.