The family of Jumonji domain containing histone demethylases 2 (JMJD2s, also known as KDM4s) demethylates lysines 9 and 36 on histone 3, resulting in the repression of specific mammalian and viral genes. ML-324 is a cell-permeable inhibitor of JMJD2E (KDM4DL; IC50 = 920 nM) that is inactive against lysine-specific demethylase, LSD1. It reduces the expression of immediate early genes of Herpes simplex virus (IC50 = ~10 μM) and human cytomegalovirus, blocks viral infection, and suppresses the level of viral reactivation in a ganglia explant model of latently infected mice. The effects of ML-324 are reversible, as viral replication resumes after drug withdrawal.
