Chaetocin

The methylation of histones by histone methyltransferases (HMT) is an important mechanism by which gene expression is stably altered during cellular differentiation and embryonic development. Chaetocin is a fungal mycotoxin that inhibits the HMT SU(VAR)3-9 (IC50 = 0.8 ?M).{18476} It inhibits other Lys9-specific HMTs, including G9a (IC50 = 2.5 ?M) and DIM5 (IC50 = 3 ?M).{18476} Selectivity for Lys9-HMTs is indicated by higher IC50 values (>90 ?M) for Lys20-specific PRSET7, Lys27-specific EZH2, and Lys4-specific SET7/9. Chaetocin potently induces cellular oxidative stress, selectively killing cancer cells and rapidly-proliferating primary cells.{18475,18476} Chaetocin’s effects on oxidative stress are, at least in part, due to its capacity to act as a competitive and selective substrate for thioredoxin reductase-1 (Km = 4.6 ?M).{18477} Chaetocin is useful both in epigenetic studies as an HMT inhibitor and in cancer research.{18398,17782,18480}