HMTase Inhibitor II, Chaetocin

A naturally occurring cell-permeable Chaetomium fungal epi-dithio-diketopiperazine that potently inhibits the H3K9 histone methyltransferase activity of Drosophila melanogaster SU(VAR)3-9 and its human homologue SUV39H1 (IC₅₀ = 600 and 800 nM, respectively) in a SAM-competitive manner, while exhibiting much reduced potency against murine G9a or Neurospora crassa DIM5 H3K9 HMT (IC₅₀ = 2.5 and 3 µM, respectively) and no activity against the H3K27 HMTase activity of Drosophila E(z), the H3K4 activity of bacterial SET7/9, or the H4K20 activity of bacterial PRSET7. Although the reduction of intramolecular disulfide bonds of Chaetocin does not affect its HMTase inhibitory activity in cell-free enzymatic assays, the integrity of the disulfide bonds is shown to be essential for its cellular uptake. Myeloma cell lines as well as myeloma cells isolated from patients are shown to be especially susceptible to death upon H₂O₂ or Chaetocin treatment due to their heightened sensitivity to cellular oxidative stress induced by these agents.

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Isham, C.R., et al. 2007. Blood109, 2579.
Greiner, D., et al. 2005. Nat. Chem. Biol.1, 143.

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Toxicity: Harmful (C)