Chaetocin, a naturally occurring fungal mycotoxin extracted from Chaetomium, is a novel and non-specific inhibitor of the histone lysine methyltransferase (HMT) G9a with an IC50 of 2.5 μM. It belongs to the class of 3,6-epidithio-diketopiperazines. Chaetocin also inhibits thioredoxin reductase (TrxR) with an IC50 of 4 μM. Chaetocin was originally reported as the first lysine-specific histone methyltransferase inhibitor. Chaetocin can selectively reduce intracellular H3K9me2 and H3K9me3 levels but has no effect on other epigenetic modifications tested. In addition, Chaetocin can induce apoptosis in human melanoma cells, generating reactive oxygen species and the intrinsic mitochondrial pathway.