JIB-04 is a pyridine hydrazone that broadly inhibits Jumonji histone demethylases (IC50s values = 230, 340, 435, 445, 855 and 1,100 nM for JARID1A, JMJD2E, JMJD2B, JMJD2A, JMJD3, and JMJD2C, respectively). It does not inhibit histone deacetylases and has minimal effect on the iron-containing enzymes methylcytosine dioxygenase TET1 and hypoxia-inducible factor prolyl hydroxylase 2. JIB-04 inhibits Jumonji demethylase activity, alters gene expression, and blocks viability of cancer cells but not in patient-matched normal cells. It also inhibits Jumonji demethylase activity in cancer cells in vivo, resulting in reduced tumor burden and prolonged survival.
